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Understanding normal biology is the backbone of all biomedical science. It is essential for understanding homeostatic maintenance, predicting how biological systems respond to their environment, and recognizing disease and targets for intervention. Research on normal biological function—including emerging topics such as circadian rhythms, the microbiome, and understanding how tissues develop from progenitor cells—can help us to better define health and understand the earliest origin of disease processes. The scope of research on normal biology can range from single cell analytics to studies of entire healthy populations. Using gold standard and emerging tools, methodologies, and technologies, such research can uncover the biological factors, behaviors, lifestyle factors, social circumstances, and environmental exposures that enable the resiliency essential for sustaining wellness in the face of the aging process, stressors, and adverse influences. Gaining new knowledge about the body’s intrinsic reparative capacity will yield greater insight into the transition from health to disease. For these reasons, understanding normal biology must remain a cornerstone of NHLBI-funded research.