The essential and the most difficult goal for the implementation of pharmacotherapy in critically ill patients is to achieve the desired pharmacological effect, while minimizing side effects of drugs. The desired pharmacodynamic effect is dependent on the concentration of a drug obtained in a target tissue. Drug concentration, in turn, depends on pharmacokinetic processes which, in this group of patients, undergo significant, often difficult to predict, changes. These changes in pharmacokinetic properties of drugs may be caused by specific organ dysfunction, mainly liver or kidneys, and may be a consequence of an acute phase of inflammation, drug-drug interaction, or therapeutic intervention. Optimal use of drugs in patients of intensive care units requires a thorough understanding by physicians of the potential impact that a critical condition has on drug’s absorption, distribution, metabolism and excretion.