Testosterone (T) deficiency is a serious health concern with detrimental effects on men’s health and quality of life. It is associated with several common and costly comorbidities. Organic diseases of the testis, the pituitary, and the hypothalamus for which T therapy (TTh) is approved by the United States (U.S.) Food and Drug Administration are rare. Most cases of T deficiency in the U.S. are related to functional hypogonadism, which is defined as low T secondary to metabolic dysfunction (obesity, metabolic syndrome type 2 diabetes), depression and chronic stress, or chronic inflammatory diseases, in the absence of intrinsic structural or organic hypothalamic-pituitary-testicular (HPT) axis pathology in middle-aged or older men. In this chapter, I discuss the mechanisms leading to functional hypogonadism, its diagnosis and treatment. I argue that because of the multiple biological effects of T that produce additive benefits, TTh associated with a proper lifestyle program is the most effective long-term approach of functional hypogonadism. Clinicians should make the best-informed decision for the health of their patients.