As management of upper gastrointestinal malignancies improves, and with popularization of bariatric surgery, endoscopists are likely to meet patients with altered upper gastrointestinal anatomy. Short‐term, the surgery can cause complications like bleeding, leaks, and fistulas, and longer‐term problems such as intestinal or biliary anastomotic strictures or biliary stones can arise, all necessitating endoscopy. In addition, the usual upper gastrointestinal pathologies can also still occur. These patients pose unique challenges. To proceed, understanding the new layout of the upper gastrointestinal tract is essential. The endoscopist, armed with a clear plan for navigation, can readily diagnose and manage most commonly occurring conditions, such as marginal ulcers and proximal anastomotic strictures with standard endoscopic instruments. With complex reconstructions involving long segments of small bowel, such as Roux‐en‐Y gastric bypass, utilization of balloon‐assisted enteroscopy may be necessary, mandating modification of procedures such as endoscopic retrograde cholangiopancreatography. Successful endoscopic management of patients with altered anatomy will require prior planning and preparation to ensure the appropriate equipment, setting, and skill set is provided.