Thrombospondins (TSPs) are multifunctional matricellular glycoproteins which are involved in the regulation of angiogenesis, proliferation, apoptosis, the NO-cGMP-dependent protein kinase pathway and transforming growth factor (TGF) beta activation. The TSP family consists of 5 members, but currently only data on effects of TSP-1 and TSP-2 in renal disease are available. Both TSPs are hardly expressed within the healthy renal cortex and can be upregulated during renal disease. Using different animal models for renal disease, TSP-1 and -2 were found to be important regulators of pathophysiological changes during renal disease with similar and contrary effects. TSP-1 is a major activator for TGF-beta resulting in profibrotic effects in the injured kidney. In contrast, TSP-2 lacks the ability for its activation. Proapoptotic actions of TSP-1 were found during renal ischemia/reperfusion injury. While TSP-1 exerts proinflammatory actions, the currently available data for TSP-2 propose anti-inflammatory effects for this molecule. Both TSPs are known angiogenesis inhibitors, which could be proved for TSP-2, but antiangiogenic effects for TSP-1 were only evident by treatment with TSP-1 peptides in renal disease. In addition, TSP-2 can inhibit cell proliferation and matrix metalloproteinase 2 activity.