The finding that the cholinergic system may be present in non-neuromuscular cells and tissues was, at the beginning, not easily accepted by the scientific community (since 1970-1982). Today the entire set of cholinergic molecules and their functions in cell-to-cell communication, mediated by intracellular ion dynamics, is well-established. Nicotinic and muscarinic (nAChR, mAChR) are functionally present on different human cell types and build a part of an autocrine-proliferative network. In synthesis Ach via nAChR or mAChR appears to be involved in the regulation of vital cell functions: proliferation, differentiation, organization of the cytoskeleton, cell-cell contact, ciliary activity, migration, secretion and absorption of ions, water and mucus. Understanding the role of the non-neuronal cholinergic system in different diseases (i.e. inflammation and or cancer) needs to be clarified in more detail, in order to optimize a future targeted-therapy, as well as precautions in the design of interventional drugs.