The basic principles of quadrupole/time-of-flight (TOF) mass spectrometers are discussed. These instruments can be used for ions produced either by electrospray ionization (ESI) or by matrix-assisted laser desorption ionization (MALDI). In the most common configuration, the functions of collisional cooling, parent ion selection, and collision-induced dissociation are carried out successively in three separate quadrupoles. The ions are then injected orthogonally into a TOF spectrometer, which makes the m/z measurement. Thus, these hybrid instruments benefit from the versatile ability of quadrupoles to carry out various tasks and from the high performance of TOF spectrometers in both simple mass spectrometry (MS) and tandem (MS/MS) modes. Significantly, collisions in the initial quadrupole decouple the instrument almost completely from the ion production process, so the quadrupole/TOF spectrometer is a stable device that is relatively insensitive to variations in the ion source.