Cholelithiasis, characterized by the presence of gallstones, is a common condition in the United States, with 80% of affected individuals having no symptoms. Symptomatic gallstone disease encompasses symptomatic cholelithiasis, biliary dyskinesia, acute cholecystitis, choledocholithiasis, gallstone pancreatitis, and acute cholangitis. It often manifests as sharp, stabbing right upper quadrant or epigastric pain as well as nausea and vomiting. History, physical examination, and laboratory evaluation alone are insufficient to make an accurate diagnosis. Ultrasonography should be the first-line imaging modality for evaluating right upper quadrant pain. Symptomatic cholelithiasis is diagnosed with the confirmation of gallstones on imaging in patients presenting with classic symptoms. Clinical prediction tools such as the 2018 Tokyo guidelines for acute cholecystitis or pretest probability calculation for choledocholithiasis should be used to aid diagnosis and determine the need for further imaging. Laparoscopic cholecystectomy is the standard treatment for most forms of symptomatic gallstone disease. In cases of choledocholithiasis, intraoperative common bile duct exploration at the time of cholecystectomy or endoscopic retrograde cholangiopancreatography performed before, during, or after cholecystectomy is needed.