The coupling of high-performance liquid chromatography with mass spectrometry (HPLC-MS) is today a rapidly advancing field. In the paper, the chromatographic aspects of this coupling are reviewed. It is shown that the quantitative evaluation of resulting chromatograms, based on centralized second moment calculations of the bands rather than visual comparison with UV chromatograms, is required. The criteria for minimum influence on column performance by the interface and mass spectrometer are presented. Based on these principles, recent developments in HPLC column design are examined for their impact on HPLC-MS. Included in these developments are high-speed separations, as a consequence of small particle diameter (3 micrometers) columns and narrow tube diameter (micropacked) columns. In the latter case, the use of 200 micrometers fused-silica capillary columns with small particle diameter supports appears particularly promising. Finally, an assessment of the utility of post-column chemistries in HPLC-MS is given. The combination of these chromatographic developments with those of MS makes the future of HPLC-MS appear to be quite bright.