Necrobiosis lipoidica (NL) is a rare granulomatous disease of poorly understood etiology. NL often occurs in patients with diabetes mellitus, tends to ulcerate, and often presents a heavy burden for patients. Th1 immune response mediated by interferon-gamma, TNF-α, IL-1, 2, 6, and Th17 immune response mediated by IL-17 play an important role in the pathogenesis of NL. The pathogenesis of NL is largely understudied, but the currently available data on the NL immunogenesis have contributed to the development of a new therapeutic approach. Standard therapy for NL does not exist yet, and current therapies are often ineffective. The first-line therapy is topical corticosteroids, intradermal injections of glucocorticoids, and systemic therapy. Also, drugs to control and prevent microvascular disorders and vascular thrombosis in the lesions may be used. Systemic cyclosporine has shown good effect in severe NL associated with ulcerative lesions. Other therapies for LN include topical granulocyte-macrophage colony-stimulating factor (GM-CSF), collagen-based agents, PUVA, UVA1-phototherapy, mycophenolate mofetil, TNF-α inhibitors, anti-IL-12/IL-23 antibodies, hyperbaric oxygenation. The search for new therapies is ongoing, as literature data on the clinical efficacy of different modes are inconsistent or include a small number of patients. We present an overview of current trends in pathogenetic therapy of NL.