Pancreatitis remains the most common severe complication of endoscopic retrograde cholangiopancreatography (ERCP), and typically develops in 5-7% of patients. Although most post-ERCP pancreatitis (PEP) is mild, severe pancreatitis and its complications (including a systemic inflammatory response or the development of pseudocysts or pancreatic necrosis) can occur, and in rare cases death can result. A means of preventing PEP in all patients who undergo the procedure remains elusive. Proper patient selection for ERCP is critical to avoid unnecessary risk. Pharmacologic attempts to prevent PEP have been largely unsuccessful; encouraging results have been difficult to validate. Prophylactic stenting of the pancreatic duct and minimally traumatic cannulation techniques offer the most promise as a means of preventing PEP. This manuscript reviews risk factors for PEP as well as pharmacologic and procedural means that can be used to reduce its incidence.