Introduction Mass spectrometers are used to determine the masses of atoms, molecules, and clusters in a wide range of applications. Presently, there is a drive towards the miniaturization of such devices for use in spacecraft life support, pollution monitoring, and explosives/narcotics detection applications. For a given mass resolution, the ion flight distance (and hence the size) of a time-of-flight (TOF) mass spectrometer is related to the length of the ionization region along the flight axis. Since femtosecond pulses can ionize atoms and molecules within a very small focal volume with near unit efficiency, they are compatible with miniature mass spectrometers. We have demonstrated a general technique for compact TOF mass spectrometry using two spatially separated laser foci. The first femtosecond laser pulse ionizes a gaseous sample and the second pulse probes for the presence of a specific mass in the analyte. Our approach enables TOF mass analysis to be performed on a sub-millimetre length scale. Furthermore, the second pulse can be intense enough to explode the molecules it probes. Using such laser- induced Coulomb explosion for molecular detection yields a significant improvement in detection efficiency for large molecules. Taken together, these developments can reduce the size and complexity of miniature TOF mass spectrometers and allow the fabrication of integrated mass analyzers with relaxed voltage, vacuum, detector, and timing electronics requirements.