The coexistence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) in the same patient is referred to as overlap syndrome (OS). Patients with OS suffer more frequently from cardiovascular disease (CVD) and carry a higher risk of COPD-related exacerbations than patients with COPD alone, especially when OSA is left untreated. Based on recent evidence, triple therapy, namely inhaled corticosteroid/long-acting muscarinic antagonist/long-acting beta-agonist (ICS-LABA-LAMA), is a treatment strategy in COPD patients with a history of exacerbations and/or CVD comorbidity. While several studies have previously focused on the role of triple therapy in patients with COPD, none of these has examined the potential benefits of this treatment in patients with COPD and concomitant OSA. Moreover, it is unknown whether patients with OS should be treated with triple therapy starting from their initial assessment, since they represent a population at risk for future exacerbations, in comparison to patients with COPD alone. In this commentary, we discuss these issues and highlight the need for further studies regarding the role of triple therapy in outcomes for patients with OS.