Compare and contrast strategies remain common pedagogical practices within physiological education. With the support of an American Physiological Society Teaching Career Enhancement Award, we have developed a junior- or senior-level undergraduate curriculum for exercise physiology that compares and contrasts the physiological adaptations of chronic terrestrial exercise (TEx) and microgravity ([mu]G). We used a series of peer-reviewed publications to demonstrate that many of the physiological adaptations to TEx and [mu]G are opposite. For example, TEx typically improves cardiovascular function and orthostatic tolerance, whereas [mu]G can lead to declines in both. TEx leads to muscle hypertrophy, and [mu]G elicits muscle atrophy. TEx increases bone mineral density and red blood cell mass, whereas [mu]G decreases bone mineral density and red blood cell mass. Importantly, exercise during spaceflight remains a crucial countermeasure to limit some of these adverse physiological adaptations to [mu]G. This curriculum develops critical thinking skills by dissecting peer-reviewed articles and discussing the strengths and weaknesses associated with simulated and actual [mu]G studies. Moreover, the curriculum includes studies on both animals and humans, providing a strong translational component to the curriculum. In summary, we have developed a novel space physiology curriculum delivered during the final weeks of an exercise physiology course in which students gain critical new knowledge that reinforces key concepts presented throughout the semester.