(CNN)For Serena it's a vital match in her quest for the grand slam while for Venus it's maybe her last chance to win Wimbledon.
Wimbledon 2015: Williams sisters ready for Centre Court showdown
But for both the Williams, Monday's sisterly showdown on Centre Court is a match neither is truly relishing.
Serena's coach Patrick Mouratoglou told CNN that the world number one would indeed rather she be facing another opponent.
"They're super close so this is not something she likes," the Frenchman revealed.
"Plus Venus is a super player. She's been No.1. She's won many grand slams and she's super dangerous on grass. But I guess if you want to win a grand slam you have to beat the best players and Venus is one of those. So she will have to beat her if she wants to win here."
Serena, who survived by the skin of her teeth in a third round classic against Britain's Heather Watson, said after that victory that if she was a neutral spectator she would be backing Venus to win their fourth round match.
"I would be rooting for Venus. She's been through so much. She's had a wonderful story.
"She's been so inspiring to me; she's just an incredible individual.
"She's just so amazing. She's been so inspiring to a lot of people with the same things that she goes through, too."
The 20-time grand slam champion was referring to her 35-year-old sibling's battle with the auto-immune disease Sjogren's syndrome, which has coincided with a slip down the rankings.
Venus showed few signs of that in sweeping aside third round opponent Aleksandra Krunic, but admitted that she was still her sister's biggest fan and there would be mixed emotions as they step out on court in opposition.
"I think we probably have the most respect for each other than anyone else on the tour.
"We both want each other to win when we're not playing each other. So there's a difference. Whereas other players, I'm not watching whether they win or lose," she said.
Mouratoglou has guided his charge to recent unprecedented success and if she can win Wimbledon it will mean she holds all four grand slams and will be three quarters of the way to a 2015 calendar grand slam.
But he admitted that Serena's only glimpse of fallibility came as a result of her own internal battles.
"I always say the same, but the biggest opponent of Serena is Serena," he said.
"I think that when she's on, when the mind is on and the preparation is great, when she's ready, she's the best player in the world.
"It's the real challenge to be able to be focused and playing well enough to pass round after round in the grand slams and if Serena can do it maybe she can do something incredible."
Mouratoglou has bad news for Serena's immediate challengers, who might believe the 33-year-old is ready to rest on her laurels up after her incredible career.
"She always wants to improve. We're working everyday on developing new things in her game.
"She has this talent for winning so I don't see any reason why she should not stay No.1 if she keeps the motivation and she stays healthy."
But first will come the sisterly battle, probably the highlight of a mouthwatering Monday program at the grass court showpiece.
It is their first match at this level in six years, when Serena ended Venus's two-year reign as Wimbledon champion in the 2009 final.
Back then, both were coached by their father Richard and he still has a prominent role within Venus' team.
By contrast, Serena has also put her faith in Mouratoglou, who admitted he had to win over her outspoken father in the transition.
"We had like a bit of a fight, no fight is too much, but I showed him that he couldn't speak to me like this and I think he liked it. He liked it because he liked the face that he saw that I had guts."
He went on: "Actually when we started working together with Serena, that's the first thing she said to me. She said: "Oh you say a lot of things like my father." And after I was talking to him I realized that on many, many things we were thinking the same.
"Probably because she feels it's not a break from the past, it's just the continuation of the work she's always done maybe with a different view but not that different."
Venus is full of pride for her sister's recent achievements while keen to add to her own tally of seven grand slam titles.
"I'm definitely just amazed at everything she's accomplished. It's exciting. It's exciting to see this happen for her, and for us as a family really. It's Serena and I and mom and dad and all of us."