CCAAT/enhancer-binding protein delta (CEBPD), as an evolutionarily conserved protein in mammals, belongs to the CEBP transcription factor family, which modulates many biological processes. The diversity of CEBPD functions partly depends on the cell type and cellular context. Aberrant CEBPD expression and activity are associated with multiple organ diseases, including cardiovascular diseases. In this review, we describe the basic molecular biology of CEBPD to understand its expression regulation, modifications, and functions. Here, we summarize the recent advances in genetically modified animals with CEBPD. Finally, we discuss the contribution of CEBPD to cardiovascular diseases and highlight the strategies for developing novel therapies targeting CEBPD.