Venus has only beaten Serena once since 2009, but the younger sister has just returned after becoming a mother. They were supposed to meet in a semifinal in 2001, but Venus pulled out due to a knee injury.
She cited tendinitis in her knee as her reason for pulling out of the tournament.
The 36-year-old professional tennis player - who has five-month-old daughter Alexis Olympia with her husband Alexis Ohanian - is reportedly planning to launch a range of beauty products under the name "Aneres", which is Serena spelled backwards.
Five-time Grand Slam champion Sharapova is a five-time finalist in Miami but has never won the tournament.
"Obviously, I wish it was anybody else in the draw, literally anybody, but that's okay", Serena said ahead of the match.
"That's, you know, totally gone out of my mind", Serena said Saturday. In fact, it's the first time they've met before the Round of 16 since their very first head-to-head matchup more than 20 years ago.
Venus and Serena are scheduled to face each other after 2 p.m. ET on Monday, live on the Tennis Channel and streaming online at WatchESPN. Since she is also not one to shy away from a new 'do and loves experimenting with her hairstyles on and off the court, perhaps some hair care products will be in the mix.
"The false allegations - that our matches were fixed - hurt, cut and ripped into us deeply". "The undercurrent of racism was painful, confusing and unfair".
The sisters first played each other competitively at the Australian Open way back in 1998, with Venus triumphing in straight sets.
With 28 previous meetings and a 29th on the way, Venus and Serena have never played anyone else as much - Serena's next-most-played opponents are Victoria Azarenka and Maria Sharapova (21 times each) and Venus' next-most-played opponent is Lindsay Davenport (27 times). "So, yeah, I didn't watch any".
"So if she makes a mistake, a little bit of me dies".