The decision to stay with a treatment or switch to a different one depends on the balance between overall effectiveness, efficacy, and tolerability. One of the challenges with antipsychotic medication treatment of serious mental illness is the risk of weight gain, which can be considerable for some patients. This article reviews the issue of weight gain associated with antipsychotics and places it within the context of metabolic issues in general. The concept of "number needed to treat" is introduced to interpret the results of the Clinical Antipsychotic Trials of Intervention Effectiveness for schizophrenia, particularly to examine the balance between overall effectiveness, efficacy, and tolerability of the different antipsychotic treatments tested. Predictors of weight gain for olanzapine are reviewed for schizophrenia and bipolar disorder, as is a monitoring plan applicable for all patients receiving antipsychotic therapy.