In the last half century, endotherapy for pancreatic diseases has changed considerably. Although endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) were introduced initially as diagnostic tools, they quickly evolved into therapeutic tools for preventing and managing complications of pancreatitis. More recently, therapeutic endoscopy has shown potential in palliation and cure of pancreatic neoplasms. This article discusses the changing landscape of pancreatic endotherapy as therapeutic ERCP and EUS were introduced and because they have evolved to treat different diseases.