Experience reveals that there is significant noncompliance with self-administered medication, especially in chronic conditions such as cancer. Noncompliance transcends the boundary of disease categories and age group. However, this is most prevalent during the adolescent years when the process of transition from parental dependency to autonomy produces confusion as to who is responsible for administration of medication. Noncompliance can result in the misjudgment of efficacy of a drug or regimen that may necessitate additional tests, alteration of dose, treatment course, and hospitalization. Currently in the United States, a large percentage of pediatric cancer patients are treated according to research protocols. In a research setting, noncompliance can result in erroneous or inconsistent findings, potentially affecting investigational results. With the availability of venous access ports and sophisticated, yet easy-to-operate pumps, increasingly, it is possible to administer parenteral medications at home. This adds a new dimension to the self-administration of medication that previously concerned mainly oral therapy. Various factors concerning the patient, disease, health providers, and treatment characteristics determine how well a given regimen is adhered to. Because a significant number of determinants are involved, it is often not possible, with any degree of certainty, to identify noncompliers or to predict the level of patient adherence to the treatment. Major factors in any successful therapy include the availability of effective medications and compliance with therapy regimen. With the advent of more successful treatments for childhood and adolescent cancer, the compliance factor is gaining greater importance because therapy currently is given with curative, rather than palliative intent. The availability of questionnaires, tests, and devices can help, to some extent, examine the degree of patient compliance. Family and social support, individualized programs, reminders to reduce forgetfulness, personalized needs assessment, and education can reduce noncompliance. Compliance is a complex and multifaceted issue that is still poorly understood and requires further investigation.