Anders and colleagues have developed a new method called Chem–seq to determine the genomic sites where small molecules interact with target proteins or DNA. Similarly to chromatin immunoprecipitation followed by sequencing (ChIP–seq), Chem–seq integrates ligand affinity capture with massively parallel DNA sequencing. Together with other genome-wide analysis techniques such as ChIP–seq, mapping the interaction sites of small-molecule drugs may provide insights into their mechanisms of action and their specificity.