Low compliance to prescribed medical interventions is an ever present and complex problem, especially for patients with a chronic illness. With increasing numbers of medications shown to do more good than harm when taken as prescibed, low compliance is a major problem in health care. Relevant studies were retrieved through comprehensive searches of different database systems to enable a thorough assessment of the major issues in compliance to prescribed medical interventions. The term compliance is the main term used in this review because the majority of papers reviewed used this term. Three decades have passed since the first workshop on compliance research. It is timely to pause and to reflect on the accumulated knowledge. The enormous amount of quantitative research undertaken is of variable methodological quality, with no gold standard for the measurement of compliance and it is often not clear which type of non-compliance is being studied. Many authors do not even feel the need to define adherence. Often absent in the research on compliance is the patient, although the concordance model points at the importance of the patient's agreement and harmony in the doctor-patient relationship. The backbone of the concordance model is the patient as a decision maker and a cornerstone is professional empathy. Recently, some qualitative research has identified important issues such as the quality of the doctor-patient relationship and patient health beliefs in this context. Because non-compliance remains a major health problem, more high quality studies are needed to assess these aspects and systematic reviews/meta-analyses are required to study the effects of compliance in enhancing the effects of interventions.