The development of desired multitarget agents may provide an attractive and cost-effective complement or alternative to drug combinations. BET and HDAC, as important epigenetic modulators, are both attractive targets in drug discovery and development. Considering the fact that BET and HDAC inhibitors exert a synergistic effect on cellular processes in cancer cells, the design of dual BET/HDAC inhibitors may be a rational strategy to improve the efficacy of their single-target drugs for tumor treatment. In current review, we depict the development of dual BET/HDAC inhibitors and particularly highlight their SARs, binding modes and biological functions with the aim to facilitate rational design and develop more dual BET/HDAC inhibitors.