•The fourth generation coupled platform of mass spectrometry (MS) is described.•The recent applications of chip-MS in proteomics and cell analysis are reviewed.•Chip-MS is an emerging platform for biological analysis. Microchip-mass spectrometry (chip-MS) has been emerging as an excellent analytical tool in the analysis of complex biological samples. The microchip can play an important role, as in cell culture and sample-preparation steps prior to mass spectral identification, which benefit from its ability to handle small sample quantities with the potential for high-throughput parallel analysis. We describe recent progress in chip-MS, including approaches that combined microchip devices with electrospray ionization and matrix-assisted laser desorption/ionization. We then review the main applications of chip-MS in proteomics and cell analysis in the past three years. We also look at the implications for the future of the field.