The clinical question about which men should receive testosterone therapy is controversial, with data from short-term clinical trials suggesting benefits for improving sexual function, strength, and well-being. What is missing from the literature are data from randomized trials that include a sufficient number of men for an adequate amount of time to assess the long-term benefits and risks of testosterone therapy. There is no study involving men that is equivalent to the Women’s Health Initiative, nor is it likely that there will be a trial of equal scale. Because testosterone therapy is available and prescribed for an estimated 2.9% of US men aged 40 years or older,1 observational data from existing cohorts of men can contribute meaningfully to assessment of therapeutic risk.