The beta-globin genes are among the most studied families of tissue-specific and developmentally regulated genes. Even before genome-wide sequencing was a reality, the sequences of extensive regions of the human, rabbit and mouse beta-globin loci were available through the individual efforts of several research groups. Many of the genomic approaches now being pursued in order to understand the control of gene expression were applied early to this gene family with success. Higher levels of regulation attributable to networks of transcription factor interaction, chromatin remodelling and enhancer-promoter communication remain as challenges in the post-genomic era.