Forming strategic partnerships is vital to academic health centers to further their missions of patient care, education, research, and community engagement. Formulating a strategy for such partnerships can be daunting due to the complexities of the health care landscape. The authors propose a game theory approach to partnership formation with the players being gatekeepers, facilitators, organizational employees, and economic buyers. Forming an academic partnership is not a game that is typically won or lost but is rather an ongoing engagement. Consistent with our game theory approach, the authors propose six basic rules to assist in successful strategic partnership formation for academic health centers.