The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway mediates multiple cellular functions critical to tumor initiation, progression, and outcomes, including growth and proliferation, metabolism, motility, migration, invasion, angiogenesis, survival, and autophagy. Tight regulation of this pathway is paramount to ensure that multiple cellular inputs are integrated for appropriate cellular outcomes. Frequent deregulation and aberrations of this pathway have been implicated in breast cancer development and progression. This review focuses on the biology of this pathway and its role in breast cancer pathogenesis. The role of therapies directed at targeting mTOR in the PI3K/Akt/mTOR pathway, which are currently being evaluated in clinical trials, will also be reviewed.