The family of AKT kinases, AKT-1, 2, and 3, collectively play a crucial role in key processes, as well as pathologic processes such as oncogenesis. The numerous AKT phosphorylation targets include proteins essential to the regulation of cell cycling, protein translation, suppression of programmed cell death, all of which, upon activation via AKT-mediated phosphorylation, promote tumor growth, survival, and aggressiveness. Activation of the AKT pathway can be immunohistochemically detected with antibodies that specifically react with phosphorylated or nonphosphorylated forms of AKT. The following review summarizes the use of phospho-AKT immunohistochemistry as a potentially valuable tool in cancer prognostication in a wide spectrum of common and uncommon malignancies, including squamous carcinoma of cervix and of head and neck; adenocarcinoma of endometrium, ovarian, breast, prostate, kidney, colon, and pancreas; carcinomas of lung and thyroid; and hematopoietic, soft tissue, and central nervous system neoplasms. To date, the findings overall suggest that the major use of p-AKT immunohistochemical staining lies in prognostication and possibly in individualization of therapy rather than in differential diagnosis.