Alicia Keys and Independent Spirit winner Patty Jenkins will also help to helm the anthology of five short films that aims to explore the impact of breast cancer.
The project will "use humour and drama to focus on the effect that breast cancer and its diagnosis has on relationships and the way women perceive themselves, while searching for strength, comfort, medical breakthroughs and, ultimately, a cure".
"Our hope with Project Five is to entertain, inform and inspire dialogue, research and prevention. Otherwise, our goals are small," said Aniston.
"We want these films to move people and empower those affected by breast cancer to stand tall through this challenge, which impacts ALL of our lives, no matter who we are. (sic)"
The Marley & Me actress will also serve as executive producer alongside her former Friends producer Marta Kauffman. Paula Wagner, Kristin Hahn, Kevin Chinoy and Francesca Silvestri will also executive produce.
A fifth director is still to be announced.
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