Epigenetic factor Brd4 has emerged as a key regulator of cancer cell proliferation. Targeted inhibition of Brd4 suppresses growth and induces apoptosis of various cancer cells. In addition to apoptosis, Brd4 has also been shown to regulate several other forms of programmed cell death (PCD), including autophagy, necroptosis, pyroptosis, and ferroptosis, with different biological outcomes. PCD plays key roles in development and tissue homeostasis by eliminating unnecessary or detrimental cells. Dysregulation of PCD is associated with various human diseases, including cancer, neurodegenerative and infectious diseases. In this review, we discussed some recent findings on how Brd4 actively regulates different forms of PCD and the therapeutic potentials of targeting Brd4 in PCD-related human diseases. A better understanding of PCD regulation would provide not only new insights into pathophysiological functions of PCD but also provide new avenues for therapy by targeting Brd4-regulated PCD.