Display omitted •Bromodomain-containing protein 4 (BRD4) is a cancer therapeutic target for synergistic combinations of drugs.•Dual-target small-molecule inhibitors of BRD4 have been discovered as cancer therapies.•We describe strategies for designing dual-target inhibitors of BRD4.•Dual-target inhibition of BRD4 is a promising strategy for drug development. Bromodomain-containing protein 4 (BRD4) is emerging as a therapeutic target that acts synergistically with other targets of small-molecule drugs in cancer. Therefore, the discovery of potential new dual-target inhibitors of BRD4 may be a promising strategy for cancer therapy. In this review, we highlight a series of strategies to design therapeutic dual-target inhibitors of BRD4 that focus on the synergistic functions of this protein. Drug combinations that exploit synthetic lethality, protein–protein interactions, functional complementarity, and blocking of resistance mechanisms could ultimately overcome the barriers inherent to the development of BRD4 inhibitors as future cancer drugs.