Obstructive sleep apnea (OSA) is associated with serious comorbid illnesses and diminished quality of life. At this time, continuous positive airway pressure (CPAP) therapy is the treatment of choice. However, only half of those individuals who accept CPAP are still using it at the end of one year. Furthermore, efficacy for improving self-reported sleepiness appears to be greater for patients with severe sleep apnea and severe sleepiness than other patient groups. Some patients, notwithstanding optimized therapy and therapeutic adherence continue experiencing excessive daytime somnolence. Consequently, other treatment modalities have developed, including oral appliances, surgery and pharmacotherapy. It is widely believed, albeit not empirically demonstrated, that an effective medication to treat OSA would elicit better acceptance and adherence than having to use a machine for many hours on a nightly basis. Nonetheless, paucity of data (i.e. lack of large-scale randomized controlled trials), variability of perceived and actual benefits, and adverse side-effects of the drugs thus far tested have prevented the use of pharmacotherapy until now. In this paper we review the outcome data from published trials designed to evaluate efficacy and safety of various medications proposed for treating obstructive sleep apnea.