In this review, we briefly analyze the current state of knowledge on histone variants and their posttranslational modifications. We place special emphasis on the description of the structural component(s) defining and determining their functional role. The information available indicates that this histone "variability" may operate at different levels: short-range "local" or long-range "global", with different functional implications. Recent work on this topic emphasizes an earlier notion that suggests that, in many instances, the functional response to histone variability is possibly the result of a synergistic structural effect.Key words: histone variants, posttranslational modifications, chromatin.