The nuclear factor I (NFI) transcription factors play important roles during normal development and have been associated with developmental abnormalities in humans. All four family members, NFIA, NFIB, NFIC and NFIX, have a homologous DNA binding domain and function by regulating cell proliferation and differentiation via the transcriptional control of their target genes. More recently, NFI genes have also been implicated in cancer based on genomic analyses and studies of animal models in a variety of tumours across multiple organ systems. However, the association between their functions in development and in cancer is not well described. In this review, we summarise the evidence suggesting a converging role for the NFI genes in development and cancer. Our review includes all cancer types in which the NFI genes are implicated, focusing predominantly on studies demonstrating their oncogenic or tumour-suppressive potential. We conclude by presenting the challenges impeding our understanding of NFI function in cancer biology, and demonstrate how a developmental perspective may contribute towards overcoming such hurdles.