BACKGROUND: Adult assimilation of lactose divides humans into dominant lactase-persistent and recessive nonpersistent phenotypes.OBJECTIVES: To review three medical parameters of lactose digestion, namely: the changing concept of lactose intolerance; the possible impact on diseases of microbial adaptation in lactase-nonpersistent populations; and the possibility that the evolution of lactase has influenced some disease pattern distributions.METHODS: A PubMed, Google Scholar and manual review of articles were used to provide a narrative review of the topic.RESULTS: The concept of lactose intolerance is changing and merging with food intolerances. Microbial adaptation to regular lactose consumption in lactase-nonpersistent individuals is supported by limited evidence. There is evidence suggestive of a relationship among geographical distributions of latitude, sunhine exposure and lactase proportional distributions worldwide.DISCUSSION: The definition of lactose intolerance has shifted away from association with lactose maldigestion. Lactose sensitivity is described equally in lactose digesters and maldigesters. The important medical consequence of withholding dairy foods could have a detrimental impact on several diseases; in addition, microbial adaptation in lactase-nonpersistent populations may alter risk for some diseases. There is suggestive evidence that the emergence of lactase persistence, together with human migrations before and after the emergence of lactase persistence, have impacted modern-day diseases.CONCLUSIONS: Lactose maldigestion and lactose intolerance are not synonymous. Withholding dairy foods is a poor method to treat lactose intolerance. Further epidemiological work could shed light on the possible effects of microbial adaptation in lactose maldigesters. The evolutionary impact of lactase may be still ongoing.