In current psychiatric practice, pharmacotherapy combinations are commonly used to treat comorbid psychiatric or medical disorders, to increase its efficacy. Although many interactions have little clinical significances, some may interfere with treatment or even be life-threatening. If the pharmacokinetic properties and pharmacodynamic mechanisms of action of the interacting drugs are known, many drug interactions can be predicted and most adverse interactions can be avoided The present review drug-drug interactions and explores underlying pharmacokinetic and pharmacodynamic considerations for interactions in psychiatric practice.