**Abstract**

The complex and extensive network of brain signals plays a vital role in maintaining physiological mechanisms and homeostasis. Acetylcholine, a chief neurotransmitter of the parasympathetic nervous system, is an important component of the cholinergic system along with cholinergic receptors, acetylcholinesterase, and choline acetyltransferase. It is responsible for mediating cell-to-cell communication and regulates various peripheral and non-neuronal cholinergic signals. Any alteration in the levels of acetylcholine leads to chronic diseases. Chronic diseases, the leading causes of disability, require continuing health care, medical attention, and potential therapeutics. This chapter will cover a brief overview of acetylcholine including its synthesis and degradation, the cholinergic system, and the influence of acetylcholine on different chronic diseases including neurological complications, metabolic disorders, cardiac diseases, and immune disorders. Moreover, the mechanistic approach of acetylcholine in different diseases and the therapies for recovering the levels of acetylcholine will be reviewed in this chapter. Further, this will illustrate the acetylcholine interaction with various cells implicated in the diseases. The insights on agonists and antagonists of acetylcholine and different targets of cholinergic receptors that could help to design better strategies to control these chronic diseases will also be provided.

**Keywords:** acetylcholine, chronic diseases, cholinergic, neurotransmitter, mechanistic approach, parasympathetic nervous system, treatment
