Thrombospondin-1 (TSP-1) is a large matricellular glycoprotein secreted by many cell types. It is a component of the extracellular matrix during active and subacute processes. Due to TSP-1's ability to interact with a variety of matrix proteins and cell-surface receptors, controversy exists about its conflicting functions. In this review, we will discuss the role of TSP-1 in human disease.