Prostate cancer is the most common nondermatologic malignancy in men. Prostate cancer is characterized by clinical and biologic heterogeneity that has complicated molecular and epidemiologic studies. Like other epithelial malignancies, prostate tumors exhibit complex karyotypic abnormalities and harbor many specific genetic alterations. Although recent work has begun to elucidate many of the specific mutations associated with prostate cancer, we still lack a clear understanding of the complement of genetic changes that suffice to program the malignant state. Here, we review our current understanding of the genetic changes found in prostate cancer and explore the connections between specific genetic alterations and malignant phenotypes including cell growth, survival, invasion, and metastasis.