Managing anticoagulation in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) is a complex clinical challenge. In this episode, we explore the delicate balance between preventing venous thromboembolism (VTE) and minimizing bleeding risks in this vulnerable population. We discuss the evolving role of direct oral anticoagulants (DOACs), including the limited and often controversial evidence supporting their use in ESRD, alongside the continued relevance of warfarin. Drawing on guideline recommendations, observational studies, and emerging research on novel agents such as Factor XI inhibitors, we highlight the nuances of decision-making and the importance of individualized therapy. Whether you’re a clinician, researcher, or learner, this episode provides a concise yet comprehensive look at where the field stands and where it’s headed.