Nuclear factor Y is a ubiquitous heterotrimeric transcription factor complex conserved across eukaryotes that binds to CCAAT boxes, one of the most common motifs found in gene promoters and enhancers. Over the last 30 years, research has revealed that the nuclear factor Y complex controls many aspects of brain development, including differentiation, axon guidance, homeostasis, disease, and most recently regeneration. However, a complete understanding of transcriptional regulatory networks, including how the nuclear factor Y complex binds to specific CCAAT boxes to perform its function remains elusive. In this review, we explore the nuclear factor Y complex's role and mode of action during brain development, as well as how genomic technologies may expand understanding of this key regulator of gene expression.