Despite increased global interest in testosterone deficiency in men and its treatment with testosterone therapy, practical aspects of care remain confusing to many practitioners. Testosterone deficiency can result from testicular dysfunction (primary hypogonadism) or hypothalamic-pituitary dysfunction (secondary hypogonadism), and be congenital or acquired. Sexual and nonsexual symptoms of testosterone deficiency can negatively affect quality of life and cause considerable general health concerns. Investigation of testosterone deficiency should be undertaken in men with symptoms of reduced libido, erectile dysfunction, depression, fatigue, poor concentration, and poor memory. Total and free testosterone are the most frequently used tests and evaluating serum concentrations of luteinizing hormone aids determination of primary versus secondary testosterone deficiency. Multiple formulations of testosterone therapy are available, but symptomatic benefits might not manifest for several weeks to many months; long-acting formulations are convenient and improve compliance. Concerns regarding cardiovascular and prostate cancer risks are not supported by current evidence, monitoring during therapy is mandatory. On balance, testosterone therapy can be considered a safe and effective treatment for testosterone deficiency.