Even though a plethora of systemic therapies have been proposed for necrobiotic xanthogranuloma (NXG), there is no systematic review on this topic in literature. To review all existing literature on the systemic therapy of NXG in order to identify the most effective therapies. All reported papers in the literature were screened for systemic treatments of NXG. Papers without proper description of the therapies, papers describing topical therapy, and articles without assessment of effectiveness were excluded. Subsequently, we analyzed 79 papers and a total of 175 cases. The most effective treatments for NXG are intravenous immunoglobulins (IVIG), corticosteroids, and combination therapies including corticosteroids. Corticosteroids and IVIG should therefore be considered first-line treatments in patients with NXG.