Barely 130 years after its first description, cholecystectomies are among the most commonly performed surgeries in the USA. The success of this operation with subsequent technical improvements, such as laparoscopic approaches, caused a paradigm shift in the management of gallstone disease. However, symptoms persist in 10-40 % of successfully operated patients. Reviewing monographs, textbooks, and articles published during the last 300 years, several important factors emerge as likely contributors to limited or poor treatment responses. Early on, clinicians recognized that cholelithiasis is quite common and thus often an incidental finding, especially if patients present with vague or atypical symptoms. Consistent with these observations, patients with such atypical symptoms are less likely to benefit from cholecystectomy. Similarly, lasting improvements are more reliably seen in patients with symptoms of presumed biliary origin and documented gallstones compared to individuals without stones, an important point in view of increasing rates of surgery for biliary dyskinesia. While cholelithiasis can cause serious complications, the overall incidence of clinically relevant problems is so low that prophylactic cholecystectomy cannot be justified. This conclusion corresponds to epidemiologic data showing that the rise in elective cholecystectomies decreased hospitalizations due to gallstone disease, but was associated with a higher volume of postoperative complications, ultimately resulting in stable combined mortality due to gallstone disease and its treatment. These trends highlight the tremendous gains in managing gallstone disease, while at the same time reminding us that the tightening rather than expanding indications for cholecystectomy may improve outcomes.