CLEC-2 is a C-type lectin-like molecule that has recently been identified as a receptor on the surface of platelets. Ligand binding by CLEC-2 promotes phosphorylation of a tyrosine in the cytoplasmic domain YXXL motif of CLEC-2 by Src kinases and further downstream signalling events trigger platelet activation and aggregation. The snake venom protein rhodocytin and the endogenous protein podoplanin have been identified as ligands. The structures of CLEC-2 and rhodocytin suggest that ligand binding could cluster CLEC-2 molecules at the platelet surface, so initiating signalling. CLEC-2 is a promising target for therapeutic strategies to inhibit platelet activity in thrombotic vascular disease.