The drug-induced QT prolongation predisposes to development of torsades de pointes (TdP) ventricular tachycardia and sudden death. The association between specific drug and development of TdP is difficult to document, therefore, QT prolongation is considered as a surrogate marker of the proarrhythmia risk. Most of the drugs prolong QT interval usually by blocking the potassium IKr current or altering trafficking of proteins forming the channel. Improved understanding of ion channel structure and kinetics and its role in repolarization has tremendous impact on understanding of the mechanisms of drug-induced QT prolongation and TdP. Proarrhythmia caused by a QT-prolonging drug occurs infrequently, and usually multiple factors need to operate to precipitate such an event including a combination of two or more drugs affecting the same pathway, hypokalemia, and possibly genetic predisposition. ECG provides unique opportunity to ensure safety of administered therapy. QT measurement is the most routine approach to a drug safety monitoring, however, there are many challenges related to methodology of measurements, accuracy of measurements, or optimal heart rate correction. Since drugs affecting repolarization not only prolong QT but also they alter T wave morphology, novel computerized methods quantifying these changes are being developed to assist physicians and drug manufacturers in monitoring safety of the drugs. The response of a patient to a drug is very individual and therefore an individualized system of drug administration and monitoring needs to be developed, which takes into account baseline QTc duration and its changes after a drug was introduced. (Cardiol J 2007; 14: 523-533)