Working memory is an ability to keep information in short-term memory and manipulate them “on line”. Working memory is also involved in complex frontal executive functions. The role of dopaminergic system in modulating working memory processes in prefrontal cortex is well established. Also the role of serotoninergic receptors is postulated. The purpose of this study was to assess the association between the polymorphisms of dopaminergic (DRD1, DRD3, DRD4, COMT) and serotoninergic (SERT – serotonin transporter, 5HT2A, 5HT2C) genes’ polymorphisms and performance on WCST in 200 volunteers from the Polish population. We found the association between DRD1, DRD4, COMT and SERT genes polymorphisms and the performance on WCST. The results obtained in the study indicate that dopaminergic and serotoninergic genes may play a role in modulating the executive function and working memory processes in healthy subjects. The pattern of this influence may be different in males and females. Moreover, the relationship between the efficacy of prefrontal cognitive function and genes polymorphisms may differ between healthy subjects and schizophrenic patients.