More than a decade after their discovery, the three AKT kinase family members have emerged as central players in the signaling cascades that regulate cell growth, proliferation, survival and various aspects of intermediary metabolism. The mechanisms of activation of AKT kinases have been defined in relatively precise terms and new substrates are currently being validated in vivo. However, it is presently unclear whether AKT1, -2 and -3 are functionally redundant or whether each one performs specific functional role(s). In this review, we will summarize the signaling properties and highlight the specificities of AKT kinases that have emerged from the study of human cancer and animal models. While AKT kinases are an attractive target for pharmacological intervention, knowledge of the precise individual roles of AKT family members will improve the design of highly specific AKT-based therapeutics having reduced toxicity and improved efficacy.