Patients with gallbladder and biliary disease may present with complaints of right upper quadrant or epigastric pain, fever, jaundice, pruritus, nausea, and vomiting, or they may be asymptomatic with only laboratory abnormalities. Ultrasound (US), multidetector computed tomography (MDCT), and magnetic resonance imaging (MRI) with or without magnetic resonance cholangiopancreatography (MRCP) may be used for noninvasive evaluation of patients with signs and symptoms of gallbladder and biliary disease. In many instances, noninvasive imaging will establish the diagnosis prior to endoscopic or surgical intervention. The differential diagnosis for these patients is broad and includes infectious, noninfectious inflammatory, neoplastic, and congenital disorders of the liver, gallbladder, and bile ducts. The purpose of this chapter is to discuss the approach to differential diagnosis of commonly encountered patterns during gallbladder and bile duct imaging: gallbladder wall thickening, gallbladder polyps and masses, extrahepatic and intrahepatic bile duct dilatation, and bile duct strictures. Diseases that cause these patterns are reviewed.