Protein quantitation by mass spectrometry (MS) is attractive since it is possible to obtain both the identification and quantitative values of novel proteins and their posttranslational modifications in one experiment. In contrast, protein arrays only provide quantitative values of targeted proteins and their modifications. There are an overwhelming number of quantitative mass spectrometry (MS) methods for protein and peptide quantitation. The aim here is to provide an overview of the most common MS-based quantitative methods used in the proteomics field and discuss the computational algorithms needed for the robust quantitation of proteins, peptides, and their posttranslational modifications.