Globally, laboratory analysis of the prohibited drugs contained in samples of urine and blood taken from athletes in and out of competition indicates that hormones comprise a significant proportion of the drugs that have been misused by athletes in attempts to improve their performance. However, confirming that an athlete has doped with some of the proscribed hormones remains a major challenge for chemists. Currently, analytical evidence is considered only the ‘tip of the iceberg’ in identifying the prevalence of the global misuse of ergogenic substances and methods. Recently, there has been a shift towards ‘non-analytical’ positives via drug seizures by customs, the athletes’ biological passport as well as other indirect evidence such as occurred with the cyclist, Lance Armstrong. Scientific evidence as to the efficacy of proscribed hormones to enhance sports performance is available for some such as testosterone and erythropoietin but not for the many others including insulin and growth hormone. It should be noted that ethical considerations often prevent scientists from undertaking such research because the quantity of proscribed drugs that many athletes self-administer is far greater that accepted therapeutic doses. But anecdotal information is available from persons who have experimented with them and tends to indicate that many of these drugs do have the potential to improve sports performance including some hormones, their releasing factors and precursors. In contrast, there are elite athletes with medical conditions that necessitate treatment with drugs such an insulin and testosterone that are proscribed in sport. For the past two decades, a mechanism has been available for committees to receive and assess application for athletes to administer these drugs and with approval, athletes can and have competed with success. These and other aspects will be discussed in detail.