Although GLC is still used with some frequency, HPLC is currently the most widely practiced chromatographic technique for the measurement of therapeutic drugs. Efficiency and selectivity can be manipulated to meet the requirements of clinical samples, especially when drug metabolites are present and their concentrations are of importance. The ability to simultaneously quantitate several drugs has led to the development of many methods for antiepileptic, antiarrhythmic, and antidepressant drugs. Selective detectors offer more sensitive analysis in many separations and are increasingly popular. The development of automated methods for sample preparation suggests that more cost-effective strategies for the chromatographic analysis of new drugs will be possible in the near future.