Prostate cancer is the most diagnosed noncutaneous malignancy and the second most common cause of cancer death among men in the United States. Risk factors include older age, family history of prostate cancer, and Black race. Screening via prostate-specific antigen testing may lead to a small reduction in prostate cancer–specific mortality, with no reduction in all-cause mortality, but it can cause significant harms related to false-positive test results, unnecessary biopsies, overdiagnosis, and overtreatment. Shared decision-making is strongly recommended by all national guidelines before initiating screening. Most guidelines recommend screening every 2 to 4 years in men 55 to 69 years of age at average risk. After a positive prostate-specific antigen test result (more than 4 ng/mL), the test should be repeated. If the prostate-specific antigen level is still elevated, next steps include multiparametric magnetic resonance imaging, assessment of urine or blood biomarkers, and referral to urology. Active surveillance is increasingly accepted as the preferred standard of care for patients with newly diagnosed low-risk prostate cancer, because it is associated with similar long-term survival and better quality of life than curative treatment. The primary intent of screening is to identify patients with clinically significant prostate cancer who may benefit from curative treatment while minimizing the detection of clinically insignificant cancer.