The physiologic mechanisms by which the four activities of sleep, sedentary behavior, light-intensity physical activity, and moderate-to-vigorous physical activity (MVPA) affect health are related, but these relationships have not been well explored in adults. Research studies have commonly evaluated how time spent in one activity affects health. Because one can only increase time in one activity by decreasing time in another, such studies cannot determine the extent that a health benefit is due to one activity versus due to reallocating time among the other activities. For example, interventions to improve sleep possibly also increase time spent in MVPA. If so, the overall effect of such interventions on risk of premature mortality is due to both more MVPA and better sleep. Further, the potential for interaction between activities to affect health outcomes is largely unexplored. For example, is there a threshold of MVPA minutes per day, above which adverse health effects of sedentary behavior are eliminated? This article considers the 24-h Activity Cycle (24-HAC) model as a paradigm for exploring inter-relatedness of health effects of the four activities. It discusses how to measure time spent in each of the four activities, as well as the analytical and statistical challenges in analyzing data based on the model, including the inevitable challenge of confounding among activities. The potential usefulness of this model is described by reviewing selected research findings that aided in the creation of the model and discussing future applications of the 24-HAC model.