Gastrointestinal stromal tumors (GISTs) are a rare type of cancer and a heterogeneous disease. The tyrosine kinase receptors KIT and the platelet-derived growth factor receptor alpha PDGFRA are the most common mutant genes of GIST. Mutation analysis is a diagnostic standard and is crucial for drug therapy with tyrosine kinase inhibitors (TKI). About 10% of patients already have metastases at first diagnosis. R0 resection is the only curative option in GIST and is therefore the therapy for localized tumors. In case of locally advanced primary tumors, neoadjuvant therapy should be offered. Recurrent, metastatic and locally advanced disease can be treated with TKI; in select cases surgical therapy may be added. The role of surgery in metastatic disease is controversial.