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Activation of phosphatidylinositol 3-kinase (PI3K)/AKT signaling is associated with endocrine resistance in estrogen receptor positive (ER+) breast cancer. AKT is an important downstream effector of the PI3K signaling pathway, regulating key cellular functions related to cancer progression and survival. Preclinical evidence supports the evaluation of AKT inhibitors as a treatment strategy for patients with ER+ breast cancer. Early phase clinical trials of AKT inhibitors provides preliminary efficacy and key toxicity profiles. Clinical trials have been focused on combining AKT inhibitors with hormonal therapy or cytotoxic chemotherapy. Here we present an update on the clinical investigation of these agents.