All organisms contain thousands of proteins and peptides in their body fluids. A deeper insight into the functional relevance of these polypeptides under different physiological and pathophysiological conditions and the discovery of specific peptide biomarkers would greatly enhance both diagnosis and therapy of specific diseases. Proteomic methods can provide means to accomplish this grand medical vision. In this review, we will focus on the potential use of proteome analysis for clinical applications, such as disease diagnosis and assessment of response to therapy. We focus on CE coupled with MS (CE-MS) and review in detail different aspects of CE-MS coupling and the results obtained using CE-MS analysis of clinically relevant samples. We also discuss clinical applications of the technology for the diagnosis of renal diseases, urogenital cancer, and arteriosclerosis as well as monitoring the responses to therapeutic interventions.