Previous studies indicate that two upstream CCAAT/enhancer-binding protein (C/EBP) sites and C/EBPbeta are required for subtype B HIV-1 gene expression in cells of the monocyte-macrophage lineage. The mechanisms of C/EBP regulation of HIV-1 transcription and replication remain unclear. This review focuses on studies concerning the role of C/EBP factors in HIV-1, human T-cell leukemia virus type 1, and SIV transcription in various cell types and tissues cultured in vitro, animal models and during human infection. The structure and function of the C/EBPbeta gene and the related protein isoforms are discussed along with the transcription factors, coactivators, viral proteins, cytokines and chemokines that affect C/EBP function.