Prostate cancer represents a significant health care burden in the United States due to its incidence, treatment-related morbidity, and cancer-specific mortality. The burden begins with prostate-specific antigen screening, which has been subject to controversy due to concerns of overdiagnosis and overtreatment. Advancements in molecular oncology have provided evidence for the inherited predisposition to prostate cancer, which could improve individualized, risk-adapted approaches to screening and mitigate the harms of routine screening. This review presents the current evidence for the genetic basis of prostate cancer and novel genetically informed, risk-adapted screening strategies for prostate cancer.