Alpha-amylase, (α-amylase) is an enzyme EC 220.127.116.11 that hydrolyses alpha bonds of large, alpha-linked polysaccharides, such as starch and glycogen, yielding shorter chains thereof, dextrins, and maltose. It is the major form of amylase found in humans and other mammals. Amylase genes are located on chromosome 1p 21 and transcribed in a tissue-specific manner; the genes that encode the salivary-type isoforms are designated AMY1, and the pancreatic-type isoforms are encoded by the genes designated AMY2. Amylase was the first enzyme discovered in 1833 and over the next two centuries only the role of amylase in carbohydrate digestion was intensively studied. However, already in the 1933 the possible role of α-amylase in the glucose metabolism/diabetes mellitus development was noted and over the next years α-amylase activity is found in various organs, tissues, and body fluids, such as bronchial secretions, secretions of the fallopian tubes, tissue extracts from normal lungs, and the female genital tract. α-Amylase activity was revealed in liver, spleen, thyroid gland, stomach, small intestine, colon and even brain. The essential levels of α-amylase activity are found also in breast milk. With all these findings the alternative theories about α-amylase roles are developing. The α-amylase importance for the proper glucose metabolism regulation is already proven, and the association of low serum amylase levels with various metabolic diseases has been shown. The anti-cancer properties of this enzyme which have been mentioned already in 1908 now are finding new evidence for different types of tumors. α-Amylase has been considered as a new energy regulator in the pathogenesis of Alzheimer’s disease and regulator of enterocytes’ proliferation and differentiation in small intestine. The new aspects of amylase participation not only in the carbohydrates’ digestion, but also in the regulation of basal metabolism pathways are revealed nowadays bringing more and more knowledge about the wisdom of nature.