Capillary electrophoresis–mass spectrometry (CE–MS) can be considered a useful analytical technique for the analysis of charged compounds in the fields of proteomics and metabolomics. Currently, the commercially available co-axial sheath–liquid interface is generally employed for coupling CE to MS in most application areas. Although it has proven to be rather robust for various proteomics, glycomics and metabolomics studies, the intrinsically low-flow separation property of CE is not effectively utilized in this set-up. In this type of interfacing the sheath–liquid (typical flow-rate between 1 and 10 µL/min) dilutes the CE effluent (flow-rate between 20 and 100 nL/min), thereby reducing the detection sensitivity. Over the past few years some significant developments that aim to overcome this limitation have been made in interfacing techniques for CE–MS, which resulted in an increased interest of CE–MS for proteomics and metabolomics. This paper provides an overview of these developments and the utility of CE–MS employing the new interfacing techniques is demonstrated by representative examples in the fields of proteomics, glycomics and metabolomics. Finally, general conclusions and perspectives are provided.