The phosphoinositide 3′ kinase signaling pathway is activated in response to a plethora of growth factors and cytokines, and initiates a cascade of signaling events primarily via the induction of specific protein-serine/threonine kinases. Interest in the pathway has been driven by its frequent aberrant activation in disease and its impact on cell fate decisions owing to roles in survival signaling and metabolic control. There have been recent advances in our understanding of the primary components of this pathway, namely phosphoinositide-dependent kinase-1, protein kinase B and glycogen synthase kinase-3, including insights into their mechanisms of regulation, substrate proteins and cellular functions.