Prostate cancer is a common malignancy in Western populations and a growing public health problem globally. Although the prevalence of prostate tumors becomes very high with age, only a small proportion of tumors are potentially lethal (aggressive) and their identification is an enduring challenge. Established risk factors include age, family history, and race, but, until the causes are better understood, prevention is impossible. In some populations, the widespread use of prostate-specific antigen (PSA) tests to increase early detection has inflated incidence, often by more than twofold, and shifted the disease spectrum toward less aggressive forms, that is, small tumors of low to moderate grade. Given the virtually ubiquitous presence of small low-grade tumors in the prostates of older men, the principal research question now is to identify factors that cause progression to advanced disease. Overdiagnosis and treatment has had ramifications for public health and has complicated efforts to identify causal factors for aggressive disease, since all prostate cancers are included as one entity in most epidemiological studies, irrespective of their potential to metastasize.