Alpha-L-fucose is a 6-carbon deoxyhexose that is commonly incorporated into human glycoproteins and glycolipids. It is found at the terminal or preterminal positions of many cell-surface oligosaccharide ligands that mediate cell-recognition and adhesion-signaling pathways. These include such normal events as early embryologic development and blood group recognition and pathologic processes including inflammation, infectious disease recognition, and neoplastic progression. Fucosylated oligosaccharide ligands mediate cell-cell adhesion through binding to cell-surface selectins (calcium-dependent binding proteins) and calcium-dependent interactions with other cell-surface carbohydrate counterligands. A number of fucose-containing "natural ligands" are common to inflammatory and malignant cell processes. We review evidence that alpha-L-fucose is critically important for cell-cell and cell-matrix adhesion in a variety of normal and pathologic processes, particularly neoplasia. Current results suggest that alpha-L-fucose provides the essential structure that enables carbohydrate ligands to bind to selectins and to carbohydrate counterligands and thereby alter cellular homeostasis.