Abstract Imatinib mesylate, an oral tyrosine kinase inhibitor, is indicated for first-line treatment of patients with unresectable and/or metastatic gastrointestinal stromal tumors (GIST). Imatinib also is approved as adjuvant therapy for patients following resection of primary GIST. Despite the efficacy of imatinib for the treatment of patients with GIST, adherence to treatment can prove difficult. Clinical studies have identified a number of factors that have a significant association with non-adherence to therapy, including age >51years, female sex, a high number of concomitant medications, and complications with patients’ therapy or the disease itself. Moreover, treatment-related adverse events and increased healthcare costs have been shown to have an impact on patients’ adherence to therapy. A study of perceptions of adherence to therapy found discrepancies between actual and perceived adherence rates; both patients and physicians overestimate adherence to treatment. Non-adherence to treatment is not exclusive to oncology, and occurs in other disease areas, particularly with chronic conditions. Evidence from other disease areas suggests that routine assessment of adherence and the implementation of adherence programs can lead to improvements in health status and reduced healthcare costs. Improving patient adherence to imatinib treatment for patients with unresectable/metastatic GIST is particularly important, because non-adherence has a significant impact on clinical outcomes and healthcare costs. Therefore, the effective management of treatment-related adverse events along with patient education may be important in keeping patients compliant with continuous therapy.