Serena has a chance to win her 50th career title. In the semi-final the American beat Sara Errani of Italy 7-5, 6-2. Sharapova won the 500th match of her career by defeating former World No1 Ana Ivanovic 6-4, 6-3.
Both players enter the final in good form and with numbers to back their bid for the title.
The match is not just about the title for the two players but also offers them a chance to take over the World No1 ranking ahead of the French Open later this month.
Sharapova has won all 10 sets she has played at the tournament, Serena on the other hand has a 12-2 record against the Russian.
The 31-year-old will play her first final on red clay since 2002. Last year's trophy for Serena at the Caja Magica came on the experimental blue clay surface that was removed following players' complaints that it was too slippery.
The Madrid Open final promises to be an explosive match as both women will go out with all guns blazing.