Despite significant advancement in the diagnosis and treatment of breast cancer, many patients succumb to this disease. The elucidation of aberrant signaling pathways that lead to breast cancer should help develop more effective therapeutic strategies. The Akt signaling pathway plays an important role in the development and progression of breast cancer. Overexpression/activation of Akt has been associated with poor prognosis and resistance to hormonal and chemotherapy. Although mutations in Akt are rare in breast cancer, the activity of Akt is regulated by hormones, growth factors, growth factor receptors, oncogenes and tumor suppressor genes that are often deregulated in breast cancer. The objective of this commentary is to discuss recent literature on how activation of Akt by various signaling pathways contributes to breast cancer and confers resistance to current therapy.