AKT/protein kinase B (PKB) is a cardinal node in diverse signaling cascades important in both normal cellular physiology and various disease states. AKT signaling regulates cell proliferation and survival, cell growth (size), glucose metabolism, cell motility and angiogenesis. Aberrant regulation of these processes result in cellular perturbations considered hallmarks of cancer, and numerous studies testify to the frequent hyperactivation of AKT signaling in many human cancers. Various oncoproteins and tumor suppressors intersect the AKT signal transduction pathway and are activated or inactivated, respectively, in cancer. This issue of Oncogene Reviews includes a collection of perspectives on the normal cellular functions of various components of the AKT pathway, as well as biological consequences of alterations of these proteins as related to tumorigenesis. Two reviews focus on AKT regulation, one of which addresses various aspects of phosphoinositide metabolism, while the other emphasizes the role of AKT-interacting proteins in AKT activation. Several reviews highlight the role of major AKT substrates involved in cellular metabolism, transcription and translation; another focuses on the role of AKT signaling in epithelial-mesenchymal transition. Also included are articles on the involvement of AKT pathway deregulation in human cancer and certain hereditary cancer syndromes, as well as in murine models of cancer based on AKT pathway activation. Additional articles discuss current approaches to identify selective inhibitors of the AKT pathway.