MS-driven proteomics has evolved over the past two decades to a high tech and high impact research field. Two distinct factors clearly influenced its expansion: the rapid growth of an arsenal of instrument and proteomic techniques that led to an explosion of high quality data and the development of software tools to analyze and interpret these data which boosted the number of scientific discoveries. In analogy with the benchmarking of new instruments and proteomic techniques, such software tools must be thoroughly tested and analyzed. Recently, new tools were developed for automatic peptide quantification in quantitative proteomic experiments. Here we present a case study where the most recent and frequently used tools are analyzed and compared.