Los Blancos have enjoyed incredible European success in recent years, but domestic trophies have been harder to find. Indeed, they have not won the Copa del Rey since 2014 and have actually only triumphed in the competition on two occasions since 1993, which is staggering for a team of their ilk.
It has not been the go-to competition for Madrid like it has been for Barca, but it might well represent the club's best chance of silverware this season.
Santiago Solari's side returned to winning ways in La Liga with a 2-1 success at Levante on Sunday night, but they are nine points off leaders Barca and only a spectacular collapse from the Catalan giants will allow Madrid back into the title race at this relatively late stage of the campaign.
Madrid are, of course, still in the Champions League; they are well placed to reach the quarter-finals having recorded a 2-1 victory at Ajax in the first leg of their last-16 tie. Los Blancos have their flaws, though, and there look to be teams in a much better position to win the European competition this season.
In terms of progression to the semi-finals of the Copa del Rey, Solari's side have overcome Melilla, Leganes and Girona. They scored seven times against Girona in the quarter-finals and will be eyeing a final against either Real Betis or Valencia.
It is a hugely important period of the season for Madrid when considering that their next two after this one are against Barca and Ajax - they will host Barca in the league this weekend, before welcoming Ajax for the second leg of their last-16 Champions League tie on March 5.
While the chance to challenge for La Liga looks to be gone, Madrid are very active in two competitions, and when considering the problems that have followed the club this season, winning the Copa del Rey, finishing second in the league and making at least the semi-finals of the Champions League would be a decent campaign.
The draw at Camp Nou earlier this month has placed the Whites in a strong position, however, and they will be looking to finish the job in front of their own supporters on Wednesday night.
Recent form: WWLWWD
Recent form (all competitions): WDWWLW
The Copa del Rey is third on the list of priorities for Barca this season, but the fact that they are so close to reaching yet another final, at Madrid's expense, makes this is a huge game for the Catalan giants.
Barca landed their 30th crown last season and have lifted the trophy in each of the last four campaigns. What's more, they have present in all but one of the last eight finals and while Madrid have been enjoying European success in recent years, Barca have been dominating on the domestic stage.
Their progression to the semi-finals of this season's Copa del Rey has taken them past Cultural Leonesa, Levante and Sevilla. It has been far from straightforward, however, with Ernesto Valverde's side losing the away legs at both Levante and Sevilla before having to turn things around on home soil.
They will not be able to have that luxury on Wednesday night and it would be fair to say that Barca have not been at their best in recent weeks, despite the fact that they have still managed to pick up decent results.
Barca will enter this match off the back of a 4-2 win over Sevilla at the weekend. The result has left them seven points clear of second-placed Atletico Madrid at the top of the table, but they needed a quite stunning performance from Lionel Messi, who scored a hat-trick, to win at the Estadio Ramon.
Before the victory over Sevilla, Barca had drawn 0-0 with Lyon in the first leg of their Champions League last-16 tie. The Spanish champions will fancy their chances of triumphing on home soil, though, and the treble is still very much on for the club at this stage of the campaign.
Valverde's team have only won two of their last six matches in all competitions, however, and as mentioned, they have needed Messi to be in spectacular form to drag his team through matches in 2019.
Luis Suarez scored against Sevilla but has been off-colour in recent weeks, while Philippe Coutinho's struggles in a Barca shirt are there for all to see. Approaching the business end of the season, Barca are not at full flow, which is a concern when considering their upcoming fixtures.
However, aside from the Spanish Super Cup, the Catalan giants have not lost to Madrid at the Bernabeu since October 2014 and know that any win or any draw higher than a 1-1 will see them advance to the final of the competition once again.
Recent form: WLWLWD
Recent form (all competitions): DDDWDW
Madrid will have their captain Sergio Ramos back and available after the centre-back missed the win over Levante on Sunday night through suspension.
Ramos for Nacho could well be the only outfield change from the team that started against Levante, with Vinicius Junior and Vazquez once again expected to support Karim Benzema in the final third of the field.
Isco is available following a back problem, but it seems unlikely that the Spaniard will even make the bench as his problems with Solari show no signs of being resolved.
Cillessen would have started between the sticks had he been fit, but the Dutchman's absence means that Marc-Andre ter Stegen will feature in goal.
Samuel Umtiti made his return from injury against Sevilla, but it seems likely that Clement Lenglet will come back into the team for this match, with Sergi Roberto also potentially replacing Nelson Semedo at right-back.
Further forward, Carles Alena is battling Arturo Vidal for the midfield spot alongside Sergio Busquets and Ivan Rakitic, while Ousmane Dembele should edge out Coutinho to start alongside Messi and Luis Suarez in the final third of the field.
Real Madrid possible starting lineup:
Navas; Carvajal, Ramos, Varane, Reguilon; Casemiro, Kroos, Modric; Vinicius, Benzema, Lucas
Barcelona possible starting lineup:
Ter Stegen; Roberto, Pique, Lenglet, Alba; Rakitic, Vidal, Busquets; Dembele, L Suarez, Messi
Head To Head
It will be the first time that Madrid have locked horns with Barca in the Copa del Rey since the final of the 2013-14 competition, where Los Blancos recorded a 2-1 victory to claim the last of their 19 trophies in the competition.
Wednesday night will bring the 240th competitive El Clasico. Madrid lead the head-to-head 95 wins to Barcelona's 93, with the remaining 51 games finishing level.
Barca thumped Madrid 5-1 at Camp Nou in the league earlier this season, while the Catalan outfit recorded a 3-0 victory when they last travelled to the Bernabeu in the league in the latter stages of 2017.
We say: Real Madrid 2-2 Barcelona
It is extremely difficult to predict what will occur on Wednesday night. A strong case could be made for both teams, but we fancy Barca to match Madrid in terms of goals, with the holders advancing to the final of the competition courtesy of an away-goals win.