This clinical case study follows the progress of a diabetic patient, “Joe,” who develops an infection and ultimately undergoes a lower extremity amputation. While recovering and undergoing rehabilitation in the months following the surgery, Joe experiences phantom pain in the area where he lost his limb and takes medication and participates in experimental virtual reality therapy to ease the symptoms. The story line provides opportunities to discuss the topics of inflammation, glucose regulation, diabetic neuropathy, and phantom pain syndrome. The case was developed for the second semester of an undergraduate anatomy and physiology course following units on the nervous, skeletal and immune systems. Prior to completing the case, students should be familiar with neural communication, pain perception, and the peripheral and central nervous systems. Students should also have a basic understanding of the inflammatory response. Implementation is flexible; the case may be guided by using the case study handout or by showing a set of video vignettes produced by the authors (or both).