OBJECTIVES: To explore the definition of therapeutic compliance and evaluate the most common factors causing therapeutic non-compliance. METHODS: A qualitative review was undertaken by a literature search of the Medline database from 1970 to 2005. The following key words were used: treatment refusal, patient compliance, patient dropouts, factors, predictors and determinants. RESULTS: A total of 7372 articles were retrieved by the literature review process. From the literature review, the most commonly accepted definition of therapeutic compliance is patient's behaviors (in terms of taking medication, following diets, or executing life style changes) coincide with health care providers' recommendation for health and medical advice.The preliminary evaluation revealed a number of factors that contributed to therapeutic noncompliance. These factors include:Patient-centered factors: demographic factors (age, gender, ethnicity, education background , marriage status ), patients' beliefs, motivation and attitude about the therapy, patient-prescriber relationship, health literacy, patients' education, physical difficulties, smoking and alcohol intake, poor quality of life, forgetfulness, a history of noncompliance.Therapy-related factors: treatment complexity, duration of the treatment period, medication side effects, degree of behavioral change required. Social and economic factors: cost, income, social support. Health care system factors. Characteristics of the disease. Broadly speaking, factors related to poor therapeutic compliance can be categorized to intentional factors and non-intentional factors. They are complicated and not fully predictive. CONCLUSION: From the review, it would appear that there are numerous studies on the issue of therapeutic noncompliance, the definition of therapeutic compliance is adequately addressed and generally accepted by the clinical communities. Regarding reasons for therapeutic non-compliance, there are many factors being reported and studied over the years, but the evidence is sometimes contradictory and variable except a few important issues. From the perspective of clinical health care delivery, therapeutic noncompliance remains a major problem in enhancing health care outcomes.