The global disparities in both surgical disease burden and access to delivery of surgical care are gaining prominence in the medical literature and media. Concurrently, there is an unprecedented groundswell in idealism and interest in global health among North American medical students and trainees in anesthesia and surgical disciplines. Many academic medical centers (AMCs) are seeking to respond by creating partnerships with teaching hospitals overseas. In this article we describe six such partnerships, as follows: (1) University of California San Francisco (UCSF) with the Bellagio Essential Surgery Group; (2) USCF with Makerere University, Uganda; (3) Vanderbilt with Baptist Medical Center, Ogbomoso, Nigeria; (4) Vanderbilt with Kijabe Hospital, Kenya; (5) University of Toronto, Hospital for Sick Children with the Ministry of Health in Botswana; and (6) Harvard (Brigham and Women's Hospital and Children's Hospital Boston) with Partners in Health in Haiti and Rwanda. Reflection on these experiences offers valuable lessons, and we make recommendations of critical components leading to success. These include the importance of relationships, emphasis on mutual learning, the need for "champions," affirming that local training needs to supersede expatriate training needs, the value of collaboration in research, adapting the mission to locally expressed needs, the need for a multidisciplinary approach, and the need to measure outcomes. We conclude that this is an era of cautious optimism and that AMCs have a critical opportunity to both shape future leaders in global surgery and address the current global disparities.