This article highlights the emerging field of chemical proteomics, a powerful technology for the study of post- and co-translational modification of proteins. Genome mapping and the study of protein post-translational modifications have revealed the astounding chemical complexity present in the proteome of even the simplest organisms. The identification and characterisation of the modifications present on specific proteins in such complex mixtures has become a central challenge for post-genomic functional studies in cell and systems biology. In the chemical proteomic approach to this problem, protein-modifying enzymes and bioorthogonal chemoselective elaboration are exploited to deliver chemical tags to specific modified residues, enabling new advances in our understanding of protein modification.