Patients with metastatic GIST are currently recommended to have life-long treatment with tyrosine kinase inhibitors (TKI). The standard first-line treatment is imatinib, which is switched to other drugs at progression or if the patient does not tolerate imatinib. The prevailing hypothesis is that imatinib and other TKIs fail to completely eradicate metastatic GIST and that progression is inevitable if imatinib treatment is discontinued. However, the SSGXVIII/AIO trial found that 3 years of adjuvant imatinib yielded both superior RFS and OS rates compared to 1 year of adjuvant imatinib, which finding does not exclude the hypothesis that sufficiently long administration of imatinib might sometimes eradicate subclinical GIST. Furthermore, a few retrospective studies have reported favorable survival outcomes with surgery of residual disease in metastatic GIST in patients responding to imatinib, and a subset (approximately 20%) of patients with advanced GIST do not progress within the first 10 years on imatinib. Imatinib treatment comes with potential side-effects and, as of now, considerable costs to the society. Therefore, discontinuation of imatinib in highly selected patients, i.e. those who have received imatinib for longer than 5 years and who have undergone metastasectomy of all macroscopic oligometastatic disease, needs to be explored as a novel treatment strategy. Discontinuation might lead to detection of durable complete remissions without imatinib or even cure.