Some forms of mastocytosis are caused by c-kit mutations which cause constitutive activation of kit kinase. Compounds that inhibit kit kinase, such as indolinones, are therefore attractive as potential therapeutic agents. A hierarchy exists in the ability of compounds to inhibit kit kinase effectively. Some compounds can inhibit ligand-induced activation of wild-type receptor but are ineffective against constitutively activated mutants. Other compounds can inhibit ligand-induced activation of wild-type kit and ligand-independent activation by juxtamembrane domain mutations but not activation by activation loop mutations. Still others effectively inhibit wild-type kit and constitutively activated kit bearing either juxtamembrane or kinase domain mutations and kill the neoplastic mast cells expressing these mutants. No therapy currently exists that specifically targets a cause of mastocytosis, but there are good reasons to believe that kit kinase inhibitors may fulfill that role someday.