CCAAT boxes are motifs found within the proximal promoter of many genes, including the human globin genes. The highly conserved nature of CCAAT box motifs within the promoter region of both α-like and β-like globin genes emphasises the functional importance of the CCAAT sequence in globin gene regulation. Mutations within the β-globin CCAAT box result in β-thalassaemia, while mutations within the distal γ-globin CCAAT box cause the Hereditary Persistence of Foetal Haemoglobin, a benign condition which results in continued γ-globin expression during adult life. Understanding the transcriptional regulation of the globin genes is of particular interest, as reactivating the foetal γ-globin gene alleviates the symptoms of β-thalassaemia and sickle cell anaemia. NF-Y is considered to be the primary activating transcription factor which binds to globin CCAAT box motifs. Here we review recruitment of NF-Y to globin CCAAT boxes and the role NF-Y plays in regulating globin gene expression. This article is part of a Special Issue entitled: Nuclear Factor Y in Development and Disease, edited by Prof. Roberto Mantovani.