Hypogonadism is common throughout the illness trajectory of patients with cancer. About two thirds of male patients with advanced cancer have hypothalamic-pituitary-gonadal dysfunction and low testosterone levels. Chronic inflammation, comorbidities, cachexia, chemotherapy, and medications such as opioids, megestrol acetate, and corticosteroids contribute to primary and secondary hypogonadism. Studies have reported increased symptom burden, diminished quality of life, and poor prognosis associated with low testosterone levels in males with cancer. The Endocrine Society has published clinical practice guidelines for replacing testosterone in symptomatic patients with chronic illness and in patients receiving opioids; however, the role of testosterone therapy specifically in patients with cancer is not addressed. This review explores the potential benefits and limitations of testosterone replacement on the basis of current evidence.