Testosterone levels decline with advancing age in men, and a number of symptoms and adverse outcomes may be associated with low testosterone levels in older men. Yet, the advantages of testosterone replacement in these men have been unclear. In 2003, an Institute of Medicine panel reviewed the evidence that testosterone supplementation is beneficial and considered it unsubstantial.1 It recommended a series of clinical trials to critically evaluate the usefulness of supplementation for several clinical indications. The T-Trials, a series of 7 linked, rigorously designed and well-executed studies, were performed to address these recommendations. The findings from 3 of these studies (addressing effects in men with symptoms related to sexual function, vigor, and physical performance) were recently published.2 The results of 2 more studies (addressing effects on bone and anemia) are reported in this issue of JAMA Internal Medicine.3,4 Together, the T-Trials represent the most definitive assessments of the potential short-term advantages of testosterone replacement in older men, but were not intended to address the equally critical issue of whether there are important long-term adverse effects. To that end, also in this issue of JAMA Internal Medicine is an article by Cheetham et al5 that reports the association of testosterone supplementation with cardiovascular events in a large, retrospective cohort study.