Infectious complications after endoscopic retrograde cholangiopancreatography (ERCP) are rare and can mainly be divided into endocarditis and sepsis/cholangitis. There still remains uncertainty about the indications, antibiotic regimens, and timing for antibiotic prophylaxis. Several guidelines for antibiotic prophylaxis have been published. It is the purpose of the present paper to make an extensive review of the literature and to yield general recommendations on antibiotic prophylaxis before ERCP. Antibiotic prophylaxis is recommended for patients at high risk for endocarditis, as well as for patients with a vascular graft less than 1 year old. For sepsis/cholangitis, prophylaxis is mostly recommended for patients with a bile duct obstruction or with a pancreatic pseudocyst. For other conditions, a case-by-case evaluation by the physician/endoscopist is still inevitable.