Two disparate paths can lead to increased performance in mass spectrometric analysis. Improvements in fundamental parameters of instrument performance can be achieved through optimized interface design, improvements in ion source and analyzer efficiency, and enhanced detector performance. Increased performance also can be achieved through a better sampling protocol, or through better chromatographic performance. Alternatively, because we are clever chemists, we might choose to alter the chemical and physical characteristics of the sample itself, however collected, to achieve a more complete transport through the sample purification/selection/chromatographic process, and to achieve better ionization through enhanced sensitivity or selectivity. This second path involves a change in either the physical or chemical form of the sample. A change in the chemical form of the sample is sample derivatization, which is the focus of this column.