The search for new therapeutic strategies for prostate and breast cancer is of significant interest. Signal transducer and activator of transcription 5a/b (Stat5a/b) controls viability and growth of prostate cancer. Nuclear active Stat5a/b expression is clustered to high grade prostate cancers, predicts early disease recurrence and promotes metastatic dissemination of prostate cancer. In breast cancer, the role of Stat5a/b is more complex. In rodent model systems, Stat5a/b may promote malignant transformation and enhance growth of the breast tumors. In contrast, Stat5a/b activation in established human breast cancer positively correlates with tumor differentiation, prevents metastatic dissemination, and predicts favorable clinical outcome of node-negative breast cancer. Here we review the molecular structure and biological functions of Stat5a/b and discuss the potential applications of Stat5a/b for therapy development and as a prognostic marker for prostate and breast cancer.