Castrate-refractory prostate cancer (CRPC), which is characterized by tumor progression despite castrate levels of testosterone, develops in many prostate cancer patients treated with androgen-deprivation therapy. Standardized guidelines for treatment of CRPC are lacking and healthcare professionals must consider several factors, including serum markers, patient age and pre-existing comorbidities when choosing between second-line hormonal therapy and chemotherapy for treatment of CRPC. It is critical for healthcare professionals involved in the care of patients with CRPC to understand and utilize the current optimal methods for defining, assessing and treating this condition.