Variceal formation and bleeding from varices are the endpoint of a series of pathophysiological events that occur in patients with cirrhosis who develop clinically significant portal hypertension. Through decades of animal model and human studies, the pathomechanisms that lead to the formation of varices and bleeding have been delineated with progressive clarity. This understanding has led to improvements in medical and interventional management of portal hypertensive events, which has eventually increased survival in patients with cirrhosis. In this chapter, we discuss the pertinent pathophysiology, molecular mechanism, and physiological as well as anatomical considerations that lead to variceal development and mechanisms of variceal bleeding.