Recent technical innovations in mass spectrometry-based techniques have resulted in a range of highly sensitive and versatile instruments for high-throughput, high-sensitive, proteome-scale profiling. This wide diversity of instrumentation commercially available for mass spectrometry-based proteomics makes the choice of instrumentation sometimes difficult. The choice of instruments depends on the biological problem and the proteomic strategy chosen for protein identification. This chapter will give a short overview of the instruments routinely used in proteomic laboratories and the technical criteria that should be considered before instrument selection.