Funded by the U.S. Department of Education, a research project was conducted to evaluate the effectiveness of video games as inquiry-based learning experiences for the science classroom. As a result, the video game, Creature Control: The Quest for Homeostasis was developed and field-tested in select middle schools in the United States. Based on Understanding by Design (UbD), the curriculum is framed around an enduring understanding that homeostasis is a balancing act maintained through the interactions of body systems with the environment. The designers constructed the curriculum as a unique hybrid of the UbD approach and the 5E learning cycle constructivist model (Engage, Explore, Explain, Elaborate, and Evaluate), using the video game as the exploratory experience in the unit.