Hypoglossal nerve stimulation (HGNS) has evolved as a novel and effective therapy for patients with moderate-to-severe obstructive sleep apnea. Despite positive published outcomes of HGNS, there exist uncertainties regarding proper patient selection, surgical technique, and the reporting of outcomes and individual factors that impact therapy effectiveness. According to current guidelines, this therapy is indicated for select patients, and recommendations are based on the Stimulation Therapy for Apnea Reduction or STAR trial. Ongoing research and physician experiences continuously improve methods to optimize the therapy. An understanding of the way in which airway anatomy, obstructive sleep apnea phenotypes, individual health status, psychological conditions, and comorbid sleep disorders influence the effectiveness of HGNS is essential to improve outcomes and expand therapy indications. This article presents discussions on current evidence, future directions, and research gaps for HGNS therapy from the 10th International Surgical Sleep Society expert research panel.