The bromodomain is a highly conserved motif of 110 amino acids that is bundled into four anti-parallel α-helices and found in proteins that interact with chromatin, such as transcription factors, histone acetylases and nucleosome remodelling complexes. Bromodomain proteins are chromatin 'readers'; they recruit chromatin-regulating enzymes, including 'writers' and 'erasers' of histone modification, to target promoters and to regulate gene expression. Conventional wisdom held that complexes involved in chromatin dynamics are not 'druggable' targets. However, small molecules that inhibit bromodomain and extraterminal (BET) proteins have been described. We examine these developments and discuss the implications for small molecule epigenetic targeting of chromatin networks in cancer.