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The challenge of biology and medicine in the 21st century is complexity. A paradigm change that is currently emerging is the idea that biology is an informational science and that biological information is mediated by dynamic biological networks. The systems approach to biology and medicine is a general category of approaches that appear to be very effective in dealing with biological complexity. It requires a cross-disciplinary environment and the effective integration of biology, technology and computation/mathematics. I will discuss my view of systems biology. Then I will discuss a systems approach to disease and demonstrate how it profoundly alters our view of medicine. This approach is centered on the simple ideal that disease arises from disease-perturbed biological networks and that the dynamically altered patterns of information expressed explain the pathophysiology of disease. Moreover, they open new systems approaches to diagnostics and therapy. I will discuss prion infection in mice as an example of a systems approach to disease and I will discuss the implications these observations have for diagnosis and therapy. My prediction is that our current largely reactive medicine will be largely replaced with predictive, preventive, personalized and participatory (P4) medicine over the next 10 to 20 years.