Gangliosides comprise a varied family of glycosphingolipid structures bearing one or more sialic acid residues. They are found in all mammalian tissues but are most abundant in the brain, where they represent the quantitatively major class of sialoglycans. As prominent molecular determinants on cell surfaces, they function as molecular-recognition partners for diverse glycan-binding proteins ranging from bacterial toxins to endogenous cell–cell adhesion molecules. Gangliosides also regulate the activity of plasma membrane proteins, including protein tyrosine kinases, by lateral association in the same membranes in which they reside. Their roles in molecular recognition and membrane protein regulation implicate gangliosides in human physiology and pathology, including infectious diseases, diabetes, cancer, and neurodegeneration. The varied structures and biosynthetic pathways of gangliosides are presented here, along with representative examples of their biological functions in health and disease.