Since the second half of the 80s the development of the Psycho-Neuro-Endocrine-Immunology concepts resulted in a change of perspective, from a separatist point of view to an unifying one, relating to the interpretation of the biological functions of the body. A key point was the recognition of the importance of continuous cross-talk between cells, organs and systems in both physiological and pathological conditions based on the fine regulation of the levels of a large number of messenger molecules.Interpreting the pathological phenomenon as an imbalance in intercellular signaling, the administration of low physiological doses of messenger molecules (which act as homeostatic modulating agents) can be considered an intriguing and innovative approach in order to restore the correct intracellular signaling and consequently to restore healthy conditions; these concepts are the milestones of Low Dose Medicine.