Publisher Summary This chapter describes the technique and its potential pitfalls as it applies to elemental and isotopic analysis of elements generally of interest to the biochemist. Inductively, coupled plasma-mass spectrometry (ICP-MS) is an instrumental technique for elemental and isotopic analysis. The commercial ICP-mass spectrometers show that ICP-MS can be widely applied for the elemental and isotopic analysis of a wide variety of substances, including biological fluids. The technique is not totally free of interferences and requires some amount of sample preparation and careful quality control in order to obtain useful information from the analysis. Because ICP-MS relies on a mass spectrometer for separation and detection of the elements, reliable isotopic information can be gathered with precision and accuracy often between 0.1% and 1%. A few examples of methods employed in current ICP-MS analysis are included in this chapter. There are several potential sources of mass discrimination in ICP-MS: the ion sampling interface, the electrostatic ion lenses, the quadrupole mass spectrometer, and the detector. Therefore, the optimal conditions for determination of a single element are not usually the best conditions for determination of a group of elements, especially if the elements have large differences in their masses.