Fixed combination psychotropics, such as a combination of a tricyclic and a typical antipsychotic, were widely prescribed a generation ago. These products were plagued by a number of problems, including serious side effects, which caused them to fall out of favor. More recently, a fixed combination of the atypical antipsychotic olanzapine and the serotonin selective reuptake inhibitor (SSRI) fluoxetine has been approved in the US for the treatment of bipolar I depression. Although the combination produced a robust clinical response relative to placebo or olanzapine alone, the response from practitioners has been mixed. The reasons for this are likely to be varied. Some practitioners who remember the earlier era of fixed combinations may simply be resistant to using products of this type. Moreover, the two constituents are available and many clinicians prescribe them independently. Finally, adverse events associated with olanzapine may make practitioners hesitant. For example, weight gain is a common side effect with olanzapine, and may be associated with hyperlipidemia or type II diabetes. Aggressive management of this problem appears to be helpful in preventing or reversing weight gain. It is not clear how weight gain is going to impact the uptake of this effective treatment. © 2006 Dove Medical Press Limited. All rights reserved.