Proteomics is a rapidly expanding field of scientific study that combines techniques in protein solubilization and separation, mass spectrometry, and genome and protein database searching. The proteome is most commonly defined as the entire complement of proteins expressed in a given cell type or tissue under a given condition. A proteomics experiment may be as simple as identifying a single protein or as complex as identifying thousands of proteins in a cell lysate. In this review, we describe the general principles of proteomics and its analytic methods and present an example of an experiment to characterize the murine reticulocyte membrane proteome. A brief summary of proteomics applications and their clinical potential and relevance to clinical pathology is also presented.