Galectin-3, a unique chimera-type member of the β-galactoside-binding soluble lectin family, is present in both normal and cancer cells and plays a crucial role in the regulation of cell adhesion. It is involved both in accelerating detachment of cells from primary tumor sites and promoting cancer cell adhesion and survival to anoikis in the blood stream. Cell adhesion molecules (CAMs) are membrane receptors that mediate cell–cell and cell–matrix interactions, and are essential for transducing intracellular signals responsible for adhesion, migration, invasion, angiogenesis, and organ-specific metastasis. This review will discuss the recent advances in our understanding the biological functions, mechanism and therapeutic implication of the interaction between galectin-3 and CAMs in cancer metastasis.