The concept of four cardinal signs of acute inflammation comes from antiquity as rubor et tumor cum calore et dolore, extended later by functio laesa (redness and swelling with heat and pain, extended later by loss of function). The contemporary understanding of this process we owe to nineteen-century milestone discoveries by Rudof Virchow, Julius Cohnheim, and Elie Metchnikoff. In twentieth century, the development of potent technological tools allowed the rapid expansion of knowledge of cells and mediators of inflammatory processes, and molecular mechanisms of their interactions. It turned out that some mediators of inflammation have both local and distant targets, among them the liver (responding by production of several acute phase reactants) and neurohormonal centres. In the last decades it has become clear that the immune system shares mediators and their receptors with the neurohormonal system of the body; thus they form a common homeostatic entity. Such an integrative view, introduced by J.Edwin Blalock, when combined with Hans Selye?s concept of stress, led to the contemporary understanding of sickness behaviour, defined by Robert Dantzer as a highly organised strategy of the organism to fight infections and to respond to other environmental stressors.