Patients with advanced chronic kidney disease (CKD) and particularly those with end-stage renal disease (ESRD) and uraemia develop disturbances of the haemostatic system. Both thrombotic and bleeding complications can occur in patients with CKD, due to imbalanced activity of platelets, leukocytes, endothelial cells, and coagulation. Chronic inflammatory processes trigger a prothrombotic state with hyperactive platelets leading to a dysregulated cellular interplay, thereby increasing the cardiovascular risk in CKD. The bleeding risk in CKD is related to impaired platelet interaction with the vessel wall, platelet aggregation and platelet-dependent coagulation, boosted by anaemia and accumulation of uraemic toxins and platelet function-interfering drugs. Especially patients on haemodialysis are paradoxically prone to suffer from thrombotic and haemorrhagic events due to altered platelet activity. With their inflammatory potential, activated platelets are also involved in the pathogenesis of thrombotic microangiopathy, immune complex-mediated renal disease, anti-glomerular basement membrane antibody-mediated nephritis, and antibody-mediated rejection after kidney transplantation. The chapter gives an overview about the mechanisms involved in thrombosis and bleeding-promoting effects of platelets in patients with CKD as well as pathogenic platelet mechanisms in haemodialysis and other renal diseases. Furthermore, the therapeutic impact of anti-platelet agents on CKD will be discussed.