Contagious diseases have been a fatal threat to humans throughout evolution. Arguably it would serve us well if we were able to learn, with high sensitivity detect, and (when appropriate) avoid sources of contagion. The nature and potency of such a behavioral defense has gained increasing interest during the last decade and is often referred to as the “behavioral immune system”. Humans ability to detect disease cues of different sorts has been of particular interest since this is the basis of a cost-efficient behavioral avoidance of pathogens. Another part of a behavioral defense is the preparatory response of the immune system itself upon the detection of disease cues. This presentation reviews our studies on sickness detection, primarily using an experimental sickness model but also natural diseases. Results indicate that already within hours of the induction of systemic inflammation by way of endotoxin human participants can detect several olfactory, visual (facial and motion) and vocal cues of sickness, which can also be integrated for a better discrimination between healthy and sick people.