The nucleosome, fundamental unit of chromatin, is composed of four basic histones, H2A, H2B, H3 and H4, around which DNA is wrapped. In order to have access to DNA, cells must modify the structure of chromatin by different known mechanisms. One such mechanism is by replacing canonical histones in the nucleosome with variants, which can confer special functions to chromatin. H2A.Z is an evolutionary conserved variant of H2A that has both a positive and a negative role on gene transcription. The mechanisms by which H2A.Z acts are still poorly understood. However, recent reports have shed some light on this subject. H2A.Z is found associated with almost 2/3 of the promoters of genes in yeast, suggesting that this histone could have a global role on gene expression by poising chromatin for activation. We review here recent literature and discuss different aspects of the biology of this histone variant.