Systemic mastocytosis is characterized by an excessive proliferation of mast cells and their accumulation in different organs. Avoidance of trigger factors leading to anaphylaxis is a general measure valid for all forms of mastocytosis. A premedication is necessary in case of surgery, anesthesia or administration of radiocontrast agents. Symptomatic treatment comprises antihistamines, anti-leukotrienes, proton pump inhibitors and topical corticosteroids. Indolent mastocytosis with refractory symptoms, the rare cases of aggressive mastocytosis with organ dysfunction and the even rarer mast cell leukemia require cytoreductive therapy. First-line agents are interferon alpha 2b and imatinib, a tyrosine kinase inhibitor. To date there is no curative treatment.