Although excessive daytime sleepiness (EDS) attributable to obstructive sleep apnea (OSA) can be resolved by consistent usage of and effective treatment (often with the use of continuous positive airway pressure therapy), 12-58% of patients report residual EDS (REDS). While REDS is difficult to treat, a proportion of cases are possibly due to reversible issues, and wake-promoting medications can prove useful for the remaining cases. Given the challenges associated with effective management of REDS and its relationship to multiple comorbidities, multidisciplinary management of patients with REDS is often recommended. Here we aim to bridge the knowledge gap on the burden, risk factors, prevalence, and potential pathophysiologic mechanisms of REDS in patients with OSA after first-line treatment. The roles of primary care physicians and sleep specialists, as well as the importance of the use of objective assessment tools for the evaluation of REDS and the effective management of comorbidities, are discussed. An update of approved treatments and emerging candidate treatments is also presented.