Metastatic castrate-resistant prostate cancer (CRPC) can occur in a patient with de novo metastatic disease who has received androgen-deprivation therapy. The initial evaluation of a patient who may have CRPC should include measurement of testosterone levels at the time of progression to confirm the presence of castrate levels of testosterone. Components of the workup include a baseline bone scan, a computed tomography scan, and a full blood panel. The follow-up of patients with metastatic CRPC should include measurement of prostate-specific antigen (PSA) levels as well as imaging studies. The most important clinical endpoint for these patients is survival, but others include symptoms, such as pain and fatigue; biochemical factors; and radiographic progression. Physicians must help manage symptoms, regardless of whether they arise from the treatment or the disease itself. For patients with metastatic CRPC, choice of treatment is driven primarily by whether the patient has asymptomatic or minimally symptomatic, versus symptomatic, disease. In this clinical roundtable monograph, experts discuss the diagnosis, prognosis, and management of patients with CRPC, with a focus on the best utilization of 4 recently approved agents: abiraterone acetate, sipuleucel-T, cabazitaxel, and denosumab.