Mental disorders affect millions of people worldwide and are associated with a huge suffering and unbearable burden for patients and their care givers. The pathophysiology of mental disorders is not fully understood. In recent years, accumulating data suggest that inflammation may play a role in the pathogenesis of these illnesses and that psychotropic drugs exert some anti-inflammatory effects. Nuclear Factor κB (NF-κB) is a cellular pathway that has a prominent influence on immune and inflammatory responses in humans. Numerous studies examined the effects of psychotropic drugs on different inflammatory mediators (particularly cytokines) both in vitro and in vivo. However, relatively few studies investigated the effects of those drugs on NF-κB. This is quite surprising considering the pivotal role of NF-κB in promoting inflammation. The aim of this article is to review the data over the effects of psychotropic drugs on the NF-κB pathway. Overall, the summarized studies suggest that some psychotropic drugs (such as lithium and imipramine) exert potent inhibitory effects on NF-κB, while the results on other drugs are not conclusive and occasionally contradicting. The discrepancy in the results of different studies seems to derive from the various experimental conditions under which the drugs were tested.