Although cells constantly adapt to external humoral cues, like cytokines and hormones, in practice, most cellular behavior is under locally guided control, via cell-cell interactions. The most prominent members of this group of molecules involved in this intercellular signaling are the galectins, a family of carbohydrate-binding proteins, which by binding specific receptors induce signaling. It has become clear that galectins are important in the pathogenesis of cardiovascular disease, in particular atherosclerosis, stroke, myocardial infarction, and heart failure. Modulation of galectin signaling holds great promise for the treatment of cardiovascular disease as evident from preclinical studies.