Much has been said about how the CD5 cell- surface molecule could positively influence the signaling cascade of essential receptors such as the antigen specific receptor for T cells and B cells. New evidences suggest however that CD5 can also negatively regulate the early tyrosine phosphorylations induced by cytoplasmic kinases, such as the ZAP-70/Syk protein tyrosine kinases, in antigen receptor signaling and lymphocyte development. An association of CD5 with the protein tyrosine phosphatase SHP-1 may be responsible giving a molecular basis to classify CD5 in the enlarging family of inhibitory receptors.