There are multiple systemic diseases that have an impact on coagulation, of which oral and maxillofacial surgeons must be cognizant. Recent evidence has supported the potential for both hypocoagulable and hypercoagulable states in patients with liver and kidney disease with an even less understood impact on prolonged bleeding in the oral cavity. These systemic diseases are not limited to diseases affecting the liver, kidney, and bone marrow; however, these diseases are common among the patient population and surgeons must be capable of making appropriate judgment and modifying care appropriately.