The simplest definition of a biomarker is a molecule that indicates an alteration in physiology from normal. A more practical definition of a biomarker would require clinical utility of this molecule. In this sense, the biomarker would specifically and sensitively reflect a disease state and could be used for diagnosis as well as for disease monitoring during and following therapy. The need for such biomarkers in all clinical fields is urgent, since the current arsenal of biomarkers is sadly deficient and, in most cases, non-specific. In this review, we discuss strategies that use a proteomics approach to identify novel biomarkers and give examples of recent studies employing these strategies.