An up-to-date introduction for the uninitiated into the various "flavors" of chemical genomics with a series of readily reproducible techniques for applications in organic chemistry, protein chemistry, and computer science, emphasizing the high-throughput approaches that are the essence of chemical genomics. The techniques range from the classic design of small molecules as affinity ligands for specific protein families, to in silico docking for computational approaches to protein-small molecule interactions, to producing highly diverse collections of proteins, carbohydrates, and small molecules for use in arrays containing large numbers of these molecules. There are also methods for the production of proteins and carbohydrates using different expression systems, for analyzing proteins using mass spectrometry, and for arraying proteins and carbohydrates on solid supports. The protocols follow the successful Methods in Molecular Biology series format, each offering step-by-step laboratory instructions, an introduction outlining the principles behind the technique, lists of the necessary equipment and reagents, and tips on troubleshooting and avoiding known pitfalls.