The thrombospondin family of molecules is expressed in many different tissues. Its expression is highly regulated by different hormones and cytokines and is developmentally controlled. It can bind to many different cell types, probably via an array of receptors which are similarly regulated. The level of thrombospondins in body fluids and their distribution in tissue change in correlation with various pathological states. It is linked to the growth of primary tumors and to metastasis, to development of the atherosclerotic plaque, to malaria infection and other diseases. The role(s) of thrombospondin(s) are by and large unknown, though specific interaction seem to affect particular cell functions. The wide-spread spatial and temporal regulation, multiple interactions and correlation with major diseases imply important roles in cell function and call for concerted effort to unravel the mystery.