Natural products are widely employed in our daily lives as food additives, pharmaceuticals, nutraceuticals, and cosmetic ingredients, among others. However, their supply has often been limited because of low-yield extraction from natural resources such as plants. To overcome this problem, metabolically engineered Escherichia coli has emerged as a cell factory for natural product biosynthesis because of many advantages including the availability of well-established tools and strategies for metabolic engineering and high cell density culture, in addition to its high growth rate. We review state-of-the-art metabolic engineering strategies for enhanced production of natural products in E. coli, together with representative examples. Future challenges and prospects of natural product biosynthesis by engineered E. coli are also discussed.