Most studies on testosterone therapy (TTh) in men with testosterone deficiency (TD) conclude with a statement that there is no information about long-term effects of TTh. If only randomized, placebo-controlled trials are considered, this may apply to every single drug used in medicine. In this chapter, we argue that there is indeed a wealth of information on the long-term benefits and safety of TTh in men with TD. We also demonstrate that, based on long-term studies that report detailed follow-up on year-to-year changes, some benefits of TTh—such as improvements in body composition—are progressive over time while others—such as reductions in fasting glucose and blood pressure—are maintained once an optimum is achieved. For instance, once normal fasting glucose is achieved, fasting glucose remains stable and is not further reduced. Once normal blood pressure is achieved, blood pressure remains stable and does not decline further. Existing real-world evidence suggests that long-term TTh is safe and provides significant health benefits in men regardless of TD etiology, and that TTh in most men with TD is a lifelong treatment.