Successful on-line interfacing of capillary electrophoresis (CE) with electrospray (ES) mass spectrometry (MS) has progressed substantially in recent years. Of particular note also is the development which has occurred in combining the more advanced capillary-based electromigration separation techniques, such as capillary gel electrophoresis (CGE), capillary isoelectric focusing (CIEF), capillary isotachophoresis (CIT), micellar electrokinetic chromatography (MEKC) and capillary electrochromatography (CEC), with ES/MS. The union of these electromigration schemes with MS detection provides a useful and sensitive analytical tool for the separation, quantitation and identification of biological, therapeutic, environmental and other important classes of chemical analytes. By making optimal use of the characteristics inherent with these separation mechanisms, greatly enhanced MS performance may be obtained. The following review summarizes the significant issues and challenges involved with CE/ES/MS analysis as well as results which have recently been obtained.