The interface of liquid phase capillary separation methods to mass spectrometry provides a very powerful tool for characterization of biological macromolecules such as proteins and peptides. For detection of capillary separations, a mass spectrometer needs to have a high sensitivity, a rapid spectral acquisition speed, high mass resolution and accuracy, and MS/MS capability. In this work, the use of an ion trap storage/reflectron time-of-flight mass spectrometer as a rapid and sensitive detector for capillary separations has been explored. A variety of capillary separation methods have been successfully developed and interfaced to this mass spectrometer. For on-line detection of capillary electrophoresis, a detection limit in the low femtomole level has been achieved with a full mass sampling rate up to 10 Hz, which represents one of the fastest full mass sampling rates reported thus far. The low detection limit and the fast sampling rate were achieved while maintaining a high mass accuracy and resolution. Also, the work reported herein is the first report on the interface of open-tubular capillary electrochromatography to mass spectrometry, including new improvements in column preparation. Also for the first time, complex protein digests have been analyzed by pressurized capillary electrochromatography using this mass detector. Further, the on-line MS/MS capability of this mass spectrometer has been explored. A rapid spectral acquisition speed, combined with a fast data analysis scheme developed in this work, made it possible to perform real time data dependent data acquisition for fast capillary separations. MS/MS spectra of multiple components could be obtained from capillary HPLC or even capillary electrophoresis separations, which would otherwise be extremely difficult to achieve for conventional mass spectrometers.