Medicine is, in its essence, decision making under uncertainty; the decisions are made about tests to be performed and treatments to be administered. Traditionally, the uncertainty in decision making was handled using expertise collected by individual providers and, more recently, systematic appraisal of research in the form of evidence-based medicine. The traditional approach has been used successfully in medicine for a very long time. However, it has substantial limitations because of the complexity of the system of the human body and healthcare. The complex systems are a network of highly coupled components intensely interacting with each other. These interactions give those systems redundancy and thus robustness to failure and, at the same time, equifinality, that is, many different causative pathways leading to the same outcome. The equifinality of the complex systems of the human body and healthcare system demand the individualization of medical care, medicine, and medical decision making. Computational models excel in modeling complex systems and, consequently, enabling individualization of medical decision making and medicine. Computational models are theory- or knowledge-based models, data-driven models, or models that combine both approaches. Data are essential, although to a different degree, for computational models to successfully represent complex systems. The individualized decision making, made possible by the computational modeling of complex systems, has the potential to revolutionize the entire spectrum of medicine from individual patient care to policymaking. This approach allows applying tests and treatments to individuals who receive a net benefit from them, for whom benefits outweigh the risk, rather than treating all individuals in a population because, on average, the population benefits. Thus, the computational modeling-enabled individualization of medical decision making has the potential to both improve health outcomes and decrease the costs of healthcare.