Noncompliance can be defined as covert nonadherence to prescribed medication used for the prophylaxis of allograft rejection and threatening impaired kidney histology or function. It is an increasingly significant long-term problem in transplantation as the failure rates from other causes have diminished. Formal approaches to diagnosis, prophylaxis, and treatment, together with a greater understanding of what should be regarded as a syndrome, are thus increasingly important components of reducing the chronic attrition of graft function and survival. It is possible to classify noncompliant behavior using four facets of the syndrome: timing, frequency, origin, and diagnostic certainty. There are a number of different ways of approaching diagnosis, such as observation of behavior through pill counting or electronic measurements of pill container opening; blood level measurement of relevant drugs; physical examination; and observation of the consequences. However, the only certainty of diagnosis comes from direct patient admission of nonadherence to the prescribed immunosuppression. It is possible to define the highest risk patients through assessment of a number of patient-, drug-, and physician-associated variables, and then to influence the outcome through education, compliance monitoring, and simplified regimens targeted to the highest risk patients. It is important for all transplant units to address the issues raised by noncompliance if the chronic loss of allografts is to be reduced.