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There is currently no pharmacotherapy for obstructive sleep apnoea ( OSA ) but there is no principled a priori reason why there should not be one. This review identifies a rational decision‐making strategy with the necessary logical underpinnings that any reasonable approach would be expected to navigate to develop a viable pharmacotherapy for  OSA . The process first involves phenotyping an individual to quantify and characterize the critical predisposing factor(s) to their  OSA  pathogenesis and identify, a priori, if the patient is likely to benefit from a pharmacotherapy that targets those factors. We then identify rational strategies to manipulate those critical predisposing factor(s), and the barriers that have to be overcome for success of any  OSA  pharmacotherapy. A new analysis then identifies candidate drug targets to manipulate the upper airway motor circuitry for  OSA  pharmacotherapy. The first conclusion is that there are two general pharmacological approaches for  OSA  treatment that are of the most potential benefit and are practically realistic, one being fairly intuitive but the second perhaps less so. The second conclusion is that after identifying the critical physiological obstacles to  OSA  pharmacotherapy, there are current therapeutic targets of high interest for future development. The final analysis provides a tabulated resource of ‘druggable’ targets that are relatively restricted to the circuitry controlling the upper airway musculature, with these candidate targets being of high priority for screening and further study. We also emphasize that a pharmacotherapy may not cure  OSA   per se , but may still be a useful adjunct to improve the effectiveness of, and adherence to, other treatment mainstays.

A resource of potential drug targets and strategic decision‐making for obstructive sleep apnoea pharmacotherapy