A critical review of applications for the period 2000-2004, taken from the Web of Knowledge database, of the technique capillary electrophoresis-electrospray ionisation-mass spectrometry (CE-ESI-MS) in drug analysis is presented. The review is concerned with molecules of mass less than 500 Da, chosen according to selected structural classes in which they give ESI signals primarily as [M+H](+) ions although other ions, such as [M-H](-), [M+Na](+), and [M+NH4](+), are also reported. These structural classes are drugs with amine-containing side chains, drugs with N-containing saturated ring structures, 1,4-benzodiazepines, other heterocyclic hypnotics, carbohydrates, sulphonylureas, anthracyclines, sulphonamides, penicillins, cephalosporins, tetracyclines, nitrocatechols, steroids, flavonoids/polyphenols, cannabinols, and miscellaneous molecules. Details are given on the fragmentations, where available, that these ionic species exhibit in-source and in ion-trap, triple quadrupole, and time of flight-mass spectrometers. The review gives a critical evaluation of these recent CE-ESI-MS analytical methods in drug analysis. Analytical information on, for example, sample concentration techniques, CE separation conditions, recoveries from biological media and limits of detection (LODs) are provided. Potential applications of CE-MS to particular drugs or drug classes are also briefly discussed in the text.