With the availability of complete genome sequences for a number of organisms, a major challenge has become to understand how chromatin and its epigenetic modifications regulate genome function. High-throughput microarray and sequencing technologies are being combined with biochemical and immunological enrichment methods to obtain genome-scale views of chromatin in a variety of organisms. The data pinpoint novel, genomic elements and expansive chromatin domains, and offer insight into the functions of histone modifications. In parallel, state-of-the-art imaging techniques are being used to investigate higher-order chromatin organization, and are beginning to bridge our understanding of chromatin biology with that of chromosome structure.