Core histones package the genome into nucleosomes and control its accessibility to transcription factors. High mobility group proteins (HMGs) are, after histones, the second most abundant chromatin proteins and exert global genomic functions in establishing active or inactive chromatin domains. It is becoming increasingly clear that they also specifically control the expression of a limited number of genes. Moreover, they contribute to the fine tuning of transcription in response to rapid environmental changes. They do so by interacting with nucleosomes, transcription factors, nucleosome-remodelling machines, and with histone H1.