MS2-based protein quantification techniques refer to tandem mass spectrometry based quantification of proteins relying on fragment ion spectra of peptides. The two main representatives of this class of quantification techniques are spectrum counting, and reporter ion based quantification. They are both widely used in proteomics, appreciated for the simplicity and swiftness of their execution. As a result, most proteome bioinformatics suites include MS2-based protein quantification modules. In this chapter, the principles of these quantification techniques are introduced, different bioinformatic implementations are presented, and a use case is demonstrated using free open source solutions. Finally, the main pitfalls of the data processing are discussed and the performance of these techniques critically evaluated. This chapter is thus a good starting point for scientists wanting to easily and critically conduct MS2-based protein quantification.