Cholinesterase is a family of two related enzymes; acetylcholinesterase (AChE, acetylcholine hydrolase, EC 3.1.1.7) and butyrylcholinesterase (BChE, acylcholine acyl hydrolase, EC 3.1.1.8). Inhibition of AChE and BChE continue to be an effective strategy for the management of mild-to-moderate forms of Alzheimer's disease. This book describes the AChE and BChE inhibition by 81 natural products isolated from a variety of sources. Most of the newly discovered natural compounds were identified as members of new classes of cholinesterases inhibitors. The inhibition kinetics, Structure-activity relationships (SAR) and molecular docking studies on both enzymes are described. The spasmolytic properties of some of these compounds on rabbit jejunum tissues and the cytotoxicity of some selected compounds from every class of inhibitors are also discussed.