A common genetically determined polymorphism in the human population leads to two distinct phenotypes in adults, lactase persistence and adult-type hypolactasia (lactase non-persistence). All healthy newborn children express high levels of lactase and are able to digest large quantities of lactose, the main carbohydrate in milk. Individuals with adult-type hypolactasia lose their lactase expression before adulthood and consequently often become lactose intolerant with associated digestive problems (e.g. diarrhoea). In contrast, lactase persistent individuals have a lifelong lactase expression and are able to digest lactose as adults. Lactase persistence can be regarded as the mutant phenotype since other mammals down-regulate their lactase expression after weaning (the postweaning decline). This phenomenon does not occur in lactase persistent individuals. The regulation of lactase expression is mainly transcriptional and it is well established that adult-type hypolactasia is inherited in an autosomal recessive manner, whereas persistence is dominant. The recent findings of single nucleotide polymorphisms associated with lactase persistence have made it possible to study the potential mechanisms underlying adult-type hypolactasia. This work has led to the identification of gene-regulatory sequences located far from the lactase gene (LCT). The present review describes the recent advances in the understanding of the regulation of lactase expression and the possible mechanisms behind adult-type hypolactasia.