The aim of this paper was to review the basic data related to the pharmacokinetic and pharmacodynamics interactions occurring in the group of psychotropic drugs used for the treatment of affective disorders. In the first part the role of a genetically determined inter-species and inter-racial variability of the isoforms of the CYP450 for the metabolism of drugs and drug interactions, is discussed. There is strong evidence from the clinical studies that inter-individual variability of drug metabolism is a frequent reason for the treatment failure or treatment side effects. Similar undesirable effects may also accompany administration of drugs inhibiting or stimulating activity of metabolic enzymes (e.g. SSRI). Other pharmacokinetic interactions related to the changes in the transportation of drugs to the receptor sites, distribution in the organism and excretion by the kidney are also presented in some detail. Pharmacodynamic interactions are exemplified by the case of RIMAs, lithium salts and antagonists at the 5HTlA receptors. Special attention is paid to the joint administration of lithium with other psychotropic agents, mostly because of its intraneuronal site of action, related to the changes in the turnover rate of membrane’s phospholipids. The growing interest of clinicians in combining antidepressants with 5HTlA receptor antagonists for the treatment of depression is also underlined. Such therapy, firmly supported by basic science, is considered to accelerate the improvement of a mental state of depressed patients. In conclusion it is suggested that the determination of a phenotype or genotype profile of non-responders should become a standard procedure helping to solve the therapeutic problems. Such examination, performed only once in a life, may help to make the therapy more effective and less expensive by shortening the hospitalization time of the patients. Further studies on pharmacodynamic interactions open the possibilities of introducing new therapies of mental disorders to the clinic. Thus, there is little doubt left that drug-interactions should not be associated with drug side effects only.