Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Among the numerous proposed etiologies, Borrelia burgdorferi (a causative agent of Lyme disease) has been associated with MS. Although the current MS therapies decrease the quantity and severity of the attacks, most patients experience various neurologic symptoms obliging them to have recourse to one or more com- plementary and alternative medicines along with the conventional medical interventions. Among these, bee venom (BV) therapy is increasingly used for the treatment of MS; nonetheless no animal or human studies have so far revealed an improvement in the symptoms of MS upon such therapy. Herein, the authors discuss the plausible factors giving rise to the inefficacy of BV in amelioration of MS symptoms, despite its highly anti-inflammatory properties. We hypothesize that BV compound purified of phospholipase A2 that highly contains melittin and hyaluronidase may alleviate the symptoms of MS, directly through anti- inflammatory effects and degradation of hyaluronan accumulated in inflammatory demyelinating lesions, and indirectly by inhibitory effects on Borrelia burgdorferi. Thus, upon this hypothesis, we suggest that the melittin and hyaluronidase be injected into specific trigger points in the patients diagnosed with MS in randomized clinical trials to assess the efficacy of the proposed modality.