Chronic kidney disease (CKD) is associated with significant alterations in hemostasis, characterized by concurrent thrombotic and bleeding predispositions driven by endothelial dysfunction, platelet abnormalities, impaired fibrinolysis, and altered coagulation factor activity. These abnormalities, together with reduced renal clearance of several antithrombotic agents, make treatment decisions more challenging than in patients with preserved kidney function. This chapter reviews the mechanistic background and clinical evidence for aspirin, P2Y12 inhibitors, vitamin K antagonists, and direct oral anticoagulants across the CKD spectrum. Data from randomized trials, pharmacodynamic studies, observational cohorts, and CKD-specific subanalyses are integrated to highlight differences in drug responsiveness, bleeding susceptibility, and ischemic protection in mild-to-moderate CKD, advanced CKD, and dialysis-dependent populations. Special attention is given to aspirin in primary and secondary prevention, impaired clopidogrel activation, comparative outcomes of prasugrel and ticagrelor, ticagrelor-to-clopidogrel de-escalation strategies, and the evolving role of apixaban in ESKD. The evidence synthesis underscores the need for individualized, risk-adapted therapeutic decisions in this high-risk population and the limitations imposed by the scarcity of randomized data in advanced CKD.