Background:The 1995 A.S.P.E.N. Research Workshop was held at the annual meeting in Miami Beach, Florida, on January 15, 1995. The workshop focused on substrate metabolism in humans.Methods:State‐of‐the‐art presentations on the regulation of energy, carbohydrate, lipid, and protein metabolism during health and disease were made by the preeminant leaders in the field. The presentations concentrated onin vivostudies performed in humans and included both recently published and unpublished data.Results:Using sophisticated research methodology, such as nuclear magnetic resonance spectroscopy, compartmental modeling, stable isotope tracers, microdialysis, and abdominal vein catheterization, the investigators presented data that clarified unresolved issues, challenged many previously held dogmas, and raised new questions for future investigation in human intermediary metabolism.Conclusions:This workshop demonstrated thatin vivoinvestigation remains the best approach for providing physiologically relevant data in humans. An understanding of normal human physiology and the metabolic alterations caused by disease is critical for optimal nutritional and metabolic management of patients.(Journal of Parenteral and Enteral Nutrition20:13–19, 1996)