Over the past decade, our understanding of the role that Notch-signaling has in tumorigenesis has shifted from leukemogenesis into cancers of solid tumors. Emerging data suggests that in addition to direct effects mediated through the canonical Notch pathway, Notch may participate in epithelial tumor development through regulation of pathways such as PTEN/PI3K/Akt. Prostate cancer is a disease for which PTEN gene expression is especially essential. This review will summarize a role for Notch in prostate development and cancer with an emphasis on how the Notch pathway may intersect with PTEN/PI3K/Akt and mTOR signaling. © 2014 Elsevier Ltd.