Tonight's fixture is arguably the biggest meeting between these two Iberian nations in recent memory. After all, the winner of this encounter will earn themselves a place in Sunday's Euro 2012 final against either Germany or Italy.
A lot of the talk heading into this match has surrounded whether or not the Spanish rearguard will be able to stop Cristiano Ronaldo from producing some of the form that has made him favourite for this year's Ballon d'Or.
Ronaldo is unlikely to be supported by former Tottenham Hotspur striker Helder Postiga, who is nursing a hamstring injury. Instead, Hugo Almedia is expected to lead to Portuguese line in the Donbass Arena.
Meanwhile, Spain coach Vicente Del Bosque must decide whether to start Fernando Torres as a striker, or use Cesc Fabregas in that role. Some early reports have suggested that he may opt for Torres this around.
The Spanish, who headed into the tournament as defending champions, have never been beaten in the semi-final of an international competition. Meanwhile, Portugal have won just once in five attempts at this stage.
However, Paulo Bento's side can take heart from the 4-0 drubbing that they gave Spain when the sides last met in 2010. That defeat in Lisbon was the biggest that the Reds had suffered in 47 years.
Current form:
Portugal: DLLWWW
Spain: WWDWWW
Possible lineups:
Portugal: Patricio; Pereira, Pepe, Bruno Alves, Coentrao; Veloso, Raul Meireles, Moutinho, Nani; Ronaldo; Almeida
Spain: Casillas; Arbeloa, Ramos, Pique, Alba; Busquets, Alonso; Silva, Xavi, Iniesta; Torres
Sports Mole says: 1-3
