Non-adherence to medical treatment is prevalent in the context of potentially life-saving treatment for diseases such as cancer. Estimates of non-adherence to oral anti-cancer therapy range between 27% and 63% in studies of cancer patients. This represents a growing challenge, due to the paradigm shift in anti-cancer treatment from parenteral chemotherapy to oral anti-cancer drugs. The importance of adherence to medical treatment is highlighted by the World Health Organization which considers non-adherence to be a major public health concern. Studies in several malignancies have shown an adverse effect of nonadherence on treatment response, survival and quality of life, accompanied by an increase in health-care related costs. The clinical vignette accompanying this review demonstrates the complexity of management of adherence to oral anticancer therapy, through an example of an elderly chronic myeloid leukemia patient, non-adherent to serial tyrosine kinase inhibitors (imatinib, dasatinib). Her non-adherence was explained by subtle socio-demographic, patient-related and treatment-related factors, which in hindsight could have already been identified at diagnosis, resulting in preemptive management of these barriers and adherence. Routine management by the hematologist, using education alone resulted in improvement of adherence, which was predictably short-lived. Our use of a multilevel and multidisciplinary adherence-enhancing intervention, incorporating feedback based on electronic monitoring of adherence, resulted in improved adherence and treatment response in this patient. This exemplifies the contemporary evidence-based approach to non-adherence to oral-anticancer therapy.