Objective. This commentary offers a discussion of the need to consider behavioral interventions such as physical exercise as integral components of personalized medicine. Methods. We discuss the concept of personalized medicine and review existing evidence of variability in response to exercise training. Results. We argue that increased understanding is needed regarding sources of variability in exercise responsiveness, and that such understanding should lead to more tailored, often multimodal interventions. Conclusion. Studies of personalized medicine to date have primarily investigated heterogeneity in drug responsiveness; we believe it is time to begin considering preventive strategies such as exercise within a broader scope of personalized care.