ImportanceHead and neck cancer–associated lymphedema (HNCaL) affects up to 90% of survivors of head and neck cancer and is a substantial contributor to disability following head and neck cancer treatment. Despite the prevalence and morbidity associated with HNCaL, rehabilitation interventions are not well studied.ObjectiveTo identify and appraise the current evidence for rehabilitation interventions in HNCaL.Evidence ReviewFive electronic databases were searched systematically from inception to January 3, 2023, for studies on HNCaL rehabilitation interventions. Study screening, data extraction, quality rating, and risk of bias assessment were performed by 2 independent reviewers.FindingsOf 1642 citations identified, 23 studies (1.4%; n = 2147 patients) were eligible for inclusion. Six studies (26.1%) were randomized clinical trials (RCTs) and 17 (73.9%) were observational studies. Five of the 6 RCTs were published during 2020 to 2022. Most studies had fewer than 50 participants (5 of 6 RCTs; 13 of 17 observational studies). Studies were categorized by intervention type, including standard lymphedema therapy (11 studies [47.8%]) and adjunct therapy (12 studies [52.2%]). Lymphedema therapy interventions included standard complete decongestive therapy (CDT) (2 RCTs, 5 observational studies), modified CDT (3 observational studies), therapy setting (1 RCT, 2 observational studies), adherence (2 observational studies), early manual lymphatic drainage (1 RCT), and inclusion of focused exercise (1 RCT). Adjunct therapy interventions included advanced pneumatic compression devices (APCDs) (1 RCT, 5 observational studies), kinesio taping (1 RCT), photobiomodulation (1 observational study), acupuncture/moxibustion (1 observational study), and sodium selenite (1 RCT, 2 observational studies). Serious adverse events were either not found (9 [39.1%]) or not reported (14 [60.9%]). Low-quality evidence suggested the benefit of standard lymphedema therapy, particularly in the outpatient setting and with at least partial adherence. High-quality evidence was found for adjunct therapy with kinesio taping. Low-quality evidence also suggested that APCDs may be beneficial.Conclusions and RelevanceThe results of this systematic review suggest that rehabilitation interventions for HNCaL, including standard lymphedema therapy with kinesio taping and APCDs, appear to be safe and beneficial. However, more prospective, controlled, and adequately powered studies are needed to clarify the ideal type, timing, duration, and intensity of lymphedema therapy components before treatment guidelines can be established.