Current forms of mechanical treatment in obstructive sleep apnea (OSA) are generally effective in eliminating sleep and breathing disorders. However, they do have drawbacks, such as incomplete tolerability and non-compliance. Several attempts have been made to identify pharmacological treatments for OSA, but no drug has consistently reduced the severity of the condition by more than 50%. OSA, in most cases, is a condition characterized by considerable comorbidity, including hypertension, obesity, metabolic derangement and hormonal dysfunction. Daytime sleepiness and cognitive dysfunction represent common, but not consistent, findings in people with this nocturnal sleep and breathing disorder. Hence, future pharmacological treatments for OSA may need to take aspects other than the nocturnal breathing events alone into consideration. Drug research into OSA has been hampered by the lack of useful experimental systems and animal models for drug screening. In addition, the phenotypic characterization of OSA seems to be incomplete, and this limits the possibility of using stringent criteria for patient selection in drug studies. Finally, the criteria for defining the severity of OSA and disease impact seem to be insufficient for adequate definition of efficacy end points in clinical trials. This review will list some potential shortcomings and possibilities of pharmacological treatment in OSA, and discuss some of the already attempted modes of treatment.