Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are a subtype of acute-onset obsessive-compulsive disorder (OCD) thought to be caused by an autoimmune response to group A streptococcal infection. Based on this proposed pathophysiology, alternative treatments for acute-onset OCD have been introduced, including antibiotics and immunomodulatory interventions. However, the literature on treatment of PANDAS is diverse, and clinical consensus regarding optimal treatment strategy is lacking. We conducted a systematic review of articles in PubMed, Cochrane Library, and Scopus that addressed treatment for PANDAS and related disorders. Twelve research studies involving the following treatments met inclusion criteria: penicillin, azithromycin, intravenous immunoglobulin, plasma exchange, tonsillectomy, cognitive behavior therapy, NSAID and corticosteroids. In addition, 65 case reports in which patients received immunomodulatory treatments, antibiotics, and/or psychotropics were identified. We determined that rigorously conducted research regarding treatments for PANDAS is scarce, and published studies have a high risk of bias. Further research is needed in which promising treatment strategies for PANDAS and other variants of OCD with proposed autoimmune etiology are rigorously investigated.