Background Madelung's disease is a rare lipid metabolic disorder characterized by diffuse, uncapsulated lipomas in the neck, shoulder, and other areas. It mainly affects middle-aged men and is related to alcohol abuse, and the cause is not clear. Surgical treatments include lipectomy and liposuction. Methods This systematic review analyzed the treatment of Madelung's disease described in 52 articles including complete patient details, published between 2000 and 2015, and retrieved from the Web of Science, PubMed, Medline, and Embase. Results Lipectomy was performed in most cases and achieved more complete removal and better control of iatrogenic lesions of nearby structures than liposuction. Liposuction achieved good cosmetic results and is simpler and less invasive than lipectomy, but clinical experience is limited. Conclusions Both lipectomy and liposuction have advantages and drawbacks. Surgeons should base the choice of optimal treatment on patient characteristics. Novel surgical techniques and etiologically targeted treatments hold promise as future therapies.