In his celebrated monolog, the Shakespearean hero Hamlet clearly identified two extreme remedies: "To die: to sleep; no more" against "the heartache and the thousand natural shocks…" The same two functions: induction of programmed cell death ("to die") and cell cycle arrest ("to sleep"), are essential in order to antagonize the genetic insults that underlie the genesis of cancer at the cellular level. However, in the case of the protein/lipid phosphatase PTEN, the most highly mutated tumor-suppressor gene in the post-p53 era, a lot more is emerging. It is now becoming clear that PTEN plays a significant role not only in inducing cell cycle arrest and programming apoptosis, but also in other aspects of cell physiology, including the regulation of cell adhesion, migration, and differentiation.