“Nothing in Biology makes sense, except in the light of evolution.” This famous citation of Theodosius Dobzhansky also underlies the integrative field of evolutionary medicine, which faces the challenge to combine (patho-)physiological mechanisms with evolutionary function. Here we introduce a concept from the study of animal behavior, which are the four questions of Tinbergen that consider: 1. the ontogeny of an individual describing its development, 2. its physiological machinery, which 3. has fitness consequences influencing 4. the evolutionary history (phylogeny) of future generations. It is shown how this concept can be applied to infectious disease and to chronic inflammatory systemic diseases. Evolutionary medicine takes lifetime reproductive success into account. The hypothesis to be tested is that mechanisms underlying a disease in old age might have higher fitness benefits in the pre-reproductive and/or reproductive life history stage, leading to an overall increased lifetime fitness.