The field of proteomics holds great promise for identifying non-targeted, global molecular profiles ''signatures'' of normal and diseased cells. While genomics offers a wide array of tools for identifying mutated or dysregulated genes, proteomics offers the ability to measure post-translational modifications, protein stability, phosphorylation state, protein-protein interactions, and protein DNA-binding affinities. Proteomics is evolving at a fast pace, as is evident from this special issue. Strategies for protein fractionation prior to analysis are increasingly being relied upon. Selective enrichment for a subset of proteins of interest can be achieved using a variety of techniques from centrifugation procedures to affinity capture. In addition to reducing sample complexity and increasing sensitivity, strategies based on the separate analysis of subcellular compartments provide the means to determine protein location in a cell. There is clearly interest in developing robust ''industrial strength'' proteomic platforms to achieve high-throughput and high sensitivity.