The determination of beta-blockers has posed pharmaceutical analysts with a variety of problems arising from the essential characteristics of these compounds as bases and the variability of physicochemical properties of individual drugs. Liquid chromatography has become the favoured method of analysis and to a certain extent there is a standardised approach to analysis based on either solvent or solid-phase extraction and reversed-phase high-performance liquid chromatography coupled to fluorescence detection. The analyst must be aware of interactions occurring during extraction stages. All manipulations should be fully evaluated for individual drugs and metabolites prior to use. Other analytical options are chosen for specific or more demanding applications. The use of unmodified silicas for the liquid chromatography of beta-blockers (and other basic drugs) is an example of a potential alternative mode of chromatography. The stereoselectivity of the pharmacology of beta-blockers has spawned a great deal of literature describing the resolution of enantiomers by chromatographic methods. It is envisaged that this area will achieve greater prominence in the future as drug development pursues optical purity. The demand for the availability of enantiomerically pure pharmaceutical preparations will certainly see developments for preparative-scale separations as well as analytical methods and will surely promote developments in new and established methods of chromatography.