Peptidomics is the detection and identification of the peptides present in a sample, while quantitative peptidomics provides additional information about the amounts of these peptides. Comparison of peptide levels among two or more samples is termed relative quantitation. It is also possible to perform absolute quantitation of peptide levels in which the biological sample is compared to synthetic standards, which requires a separate standard for each peptide. In contrast, relative quantitation can compare levels of all peptides that are detectable in a sample, which can exceed 1000 peptides in a complex sample. In this chapter, various techniques used for quantitative peptidomics are described along with discussion of the advantages and disadvantages of each approach. A guide to selecting the optimal quantitative approach is provided, based on the goals of the experiment and the resources that are available.