OBJECTIVE: To evaluate options for the management of weight gain associated with olanzapine therapy. DATA SOURCES: MEDLINE (1966-May 2004), International Pharmaceutical Abstracts (1970-August 2003), The Cochrane Library, and EMBASE (1974-August 2003) databases were searched using the key words antipsychotics, atypical antipsychotics, olanzapine, and weight gain. Bibliographies of cited articles were reviewed. STUDY SELECTION AND DATA EXTRACTION: All articles identified from the data sources were evaluated and all information deemed relevant was included for this review. DATA SYNTHESIS: Weight gain is a common adverse effect of olanzapine, a member of the atypical antipsychotic class. Data are limited supporting a specific therapeutic approach to the management of weight gain with olanzapine treatment. Reversal of weight gain with lifestyle modifications and adjunctive pharmacologic therapies such as nizatidine and amantadine has been modest. Experience with adjunctive pharmacologic treatment has been limited to small, observational studies and case reports. Although data are limited, weight reduction has been observed in select patients switching from olanzapine to an alternative atypical antipsychotic. CONCLUSIONS: At this time, targeting lifestyle modifications provides the most reasonable approach to minimize weight gain observed with olanzapine therapy. Preliminary evidence evaluating adjunctive pharmacologic treatment for this indication has demonstrated minimal clinical benefit. Switching to an alternative atypical antipsychotic agent associated with less significant weight gain may be appropriate in select patients. Further clinical trials are needed to support a specific therapeutic approach to managing weight gain with olanzapine.