Genome sequencing projects have provided researchers with an unprecedented boon of molecular information that promises to revolutionize our understanding of life and lead to new treatments of its disorders. However, genome sequences alone offer only limited insights into the biochemical pathways that determine cell and tissue function. These complex metabolic and signaling networks are largely mediated by proteins. The vast number of uncharacterized proteins found in prokaryotic and eukaryotic systems suggests that our knowledge of cellular biochemistry is far from complete. Here, we highlight a new breed of 'postgenomic' methods that aim to assign functions to proteins through the integrated application of chemical and biological techniques.