The use of cholescintigraphy to diagnose acute cholecystitis, biliary obstruction, and biliary leakage dates back to the late 1970s. Today, despite the many advances in imaging instrumentation, radiopharmaceuticals, and methodology over these years, cholescintigraphy still plays an important role in confirming or excluding these diagnoses in acutely ill patients. Acute calculous and acalculous cholecystitis, gallbladder perforation, biliary obstruction, and biliary leakage often present as acute abdominal pain, and must be differentiated from other surgical and nonsurgical etiologies with similar symptoms and presentation. Understanding the pathophysiology of acute hepatobiliary diseases is vital for deciding on the most advantageous imaging work-up and for interpretation of the studies. To optimize the value of cholescintigraphy, up-to-date methology, proper use of appropriate pharmacologic interventions, and recognition of characteristic image findings are critical.