The regulation of gene expression is one of the most important cellular functions that determines developmental and somatic cell fates. Studies that attempt to describe the molecular interactions that govern gene regulation highlight the complexity and multidimensionality of this process. The recent explosion of information on genetic variation has added yet another dimension to this complexity. Genetic variation in elements that control gene expression directly or indirectly through interactions with other elements or molecules, contributes to observed expression level differences between individuals of the same species. In this short review we will address some of the key principles of the past and recent studies describing the degree and nature of regulatory variation with a focus on human populations.