Liquid chromatography/mass spectrometry (LC/MS) has become a routine powerful technology in clinical proteomic studies in protein identification, protein characterisation, and the discovery of biomarkers. In this chapter, we describe simple protocols for protein digestion and the analysis of digested peptides produced both by one-dimensional reversed-phase liquid chromatography and two-dimensional liquid chromatography (i.e. strong cation exchange chromatography followed by reversed-phase chromatography), coupled with tandem mass spectrometry.