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 (μG). We used a series of peer-reviewed publications to demonstrate that many of the physiological adaptations to TEx and μG are opposite. For example, TEx typically improves cardiovascular function and orthostatic tolerance, whereas μG can lead to declines in both. TEx leads to muscle hypertrophy, and μG elicits muscle atrophy. TEx increases bone mineral density and red blood cell mass, whereas μG 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 μG. This curriculum develops critical thinking skills by dissecting peer-reviewed articles and discussing the strengths and weaknesses associated with simulated and actual μG 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.