Adequate pharmacotherapy in critically ill patients is challenging for many clinicians. Disease-related pathophysiological changes often lead to complex therapy strategies including many intensive care treatments (e.g. invasive ventilation, renal replacement therapy). These measures often influence drug prescribing and dosing. Therefore, in organ dysfunction such as renal and liver impairment reduced drug elimination has to be considered by adapting drug dosing towards elimination rates. Moreover, as intensive care medicine often includes the use of multiple drugs the risk for drug-drug interactions increases. The current article gives an overview about the complexity of individual pharmacotherapy in intensive care units whilst providing information for its clinical implementation.