Maintenance therapy in bipolar disorder is primarily aimed at preventing recurrence of acute episodes. Clinicians often decide on the basis of their own experience whether mood stabilizer (MS) is properly satisfying the objective of preventing a relapse/recurrence. Evidence-based data seem far from clinical practice in assessing a MS efficacy, as they mainly focus on a drug's efficacy to first relapse and not considering the patient's course of illness. The problem of assessing MS's efficacy seems further complicated when considering combination therapy, which, due to lack of evidence-based data, economical aspects, attitude of clinicians and legal issues may bring to cumulative prescriptions. Nowadays, the drug therapy for a bipolar patient is usually tailored after longitudinal observation of his specific course of illness. The course of illness should be considered also when choosing practical criteria for the suspension of a MS due to lack of efficacy. The authors propose some preliminary criteria which may help clinicians evaluating whether a mood stabilizer is being useful or not, dividing possible outcomes and suggesting subsequent therapeutic steps in the optimization of a patient's treatment.