Management of Indolent and Smoldering SM is focused on preventing anaphylactic reactions, identifying and avoiding symptom triggers. Skin and gastrointestinal symptoms are managed with H1- and H2-antihistamines. When skin symptoms are not adequately controlled, leukotriene antagonists and oral psoralen combined with ultraviolet therapy may be added. Proton pump inhibitors, sodium cromolyn and oral corticosteroids may be added for gastrointestinal symptoms. Patients should be prescribed with self-injectable epinephrine and trained to treat recurrent cardiovascular symptoms or anaphylaxis. Depression and cognitive impairment require a psychiatric evaluation for tailored treatment. Bone involvement is managed with bisphosphonates, and eventually interferon. Omalizumab is effective on all vasomotor symptoms, including anaphylaxis, but not on respiratory, musculoskeletal, and neuropsychiatric symptoms. A cytoreductive treatment is not recommended unless anti-mediator therapy has failed. Venom immunotherapy is mandatory for patients with hymenottera venom allergy. There is not a curative option for patients with Advanced SM. The available therapeutic options include tirosin-kinase inhibitors and cladribine, with variable duration and extent of response. Imatinib mesylate was the first drug approved for SM lacking the cKIT D816V mutation; dasatinib and nilotinib are not effective. Midostaurin is active on both wild type and mutant cKIT D816V while Avapritinib is a selective cKIT D816V inhibitor: they are approved for treatment of Advanced SM. Cladribine is a purine analogue with significant activity against monocytes that were thought to have a common progenitor with mast cells. Allogeneic stem cell transplantation is usually performed in younger selected patients. MASTOCYTOSIS; THERAPY; SKIN INVOLVEMENT, SYSTEMIC MASTOCYTOSIS; TYROSINKINASEINHIBITORS; MIDOSTAURIN.