Five case studies were selected from a group of 22 patients with affective illness who have been followed during carbamazepine prophylaxis in an NIMH naturalistic prospective followup study. They highlight several factors which may be associated with relapse during maintenance treatment: (1) noncompliance; (2) breakthrough episodes with dose reduction; (3) illness exacerbation during psychosocial stress; and (4) progressive emergence of the illness or tolerance to therapeutic effects of psychotropic medications. Attention to these factors may lead to new and better management, as illustrated in case 5. The utility of a life charting approach is emphasized in delineating past and present course of illness, considering the relevance of cycling pattern and past treatment efficacy in selection of present pharmacological interventions, and helping to formulate a multifactorial concept of the interplay of biological and psychosocial factors in the evolution or exacerbation of mood disorders. Clinical recommendations and new areas of study are offered for a more comprehensive approach to maintenance treatment of affective disorders.