Maintenance of genomic diversity is critically dependent on gene regulation at the transcriptional level. This occurs via the interaction of regulatory DNA sequence motifs with DNA-binding transcription factors. The zinc finger, BED-type (ZBED) gene family contains major DNA-binding motifs present in human transcriptional factors. It encodes proteins that present markedly diverse regulatory functions. ZBED1 has similar structural and functional properties to its Drosophila homolog DNA replication-related element-binding factor (DREF) and plays a critical role in the regulation of transcription. ZBED1 regulates the expression of several genes associated with cell proliferation, including cell cycle regulation, chromatin remodeling and protein metabolism, and some genes associated with apoptosis and differentiation. In the present review, the origin, structure and functional role of ZBED1 were comprehensively assessed. In addition, the similarities and differences between ZBED1 and its Drosophila homolog DREF were highlighted, and future research directions, particularly in the area of clinical cancer, were discussed.