The identification and characterization of alterations in prostate cancer (PCa)–predisposing genes can help to inform screening strategies in undiagnosed men and treatment options in men in both the clinically localized and in the metastatic setting. This review provides an overview of the genetic basis underlying hereditary predisposition to PCa, the current role of genetics and PCa risk assessment, and how genetic risk factors affect aggressiveness and lethality of PCa.