Lactose is the preeminent soluble glycan in milk and a significant source of energy for most newborn mammals. Elongation of lactose with additional monosaccharides gives rise to a varied repertoire of free soluble glycans such as 2'-fucosyllactose (2'-FL), which is the most abundant oligosaccharide in human milk. In infants, 2'-FL is resistant to digestion and reaches the colon where it is partially fermented, behaving as soluble prebiotic fiber. Evidence also suggests that portions of small soluble milk glycans, including 2'-FL, are absorbed, thus raising the possibility of systemic biological effects. 2'-FL bears an epitope of the Secretor histo-blood group system; approximately 70-80% of all milk samples contain 2'-FL, since its synthesis depends on a fucosyltransferase that is not uniformly expressed. The fact that some infants are not exposed to 2'-FL has helped researchers to retrospectively probe for biological activities of this glycan. This review summarizes the attributes of 2'-FL in terms of its occurrence in mammalian phylogeny, its postulated biological activities, and its variability in human milk.