Traditional tobacco was originally considered to be sacred by Native Americans and was used for ceremonial and medicinal purposes for thousands of years. It was, in fact, what we know today as the Nicotiana rustica species that was considered to be “traditional” tobacco. In addition to its traditional purposes, before the arrival of Europeans, Native Americans consumed tobacco by chewing it, in a very similar manner as coca leaves. The chewing custom was gradually adopted by the new settlers, resulting in commercial production and spreading across multiple continents over time. Another indigenous way of consuming tobacco, sniffing pulverized leaves, was first brought to Europe by the Spanish in the early sixteenth century and also became popular among Europeans. The most popular method of tobacco consumption, however, is smoking cigarettes. Although it was likely nicotine that was the primary driver behind the popularity of tobacco products, there is an extremely complex biosynthetic mechanism that leads to the production of many different compounds in the tobacco plant. Without a doubt, plants are one of the most important sources of valuable compounds. Our food, paper, clothes, and numerous medicines are derived from them. Even the fossil fuels we use so much today originate from the decomposition of natural plant biomass. Common tobacco (Nicotiana tabacum L.), though primarily associated today with consumer goods production, is no different from other plants and efficiently produces variety of valuable organic compounds. This chapter describes tobacco biosynthetic potential, from alkaloids and phenolics to complex cembranoids, and presents in detail state-of-the-art knowledge of metabolic pathways as well as the methods and factors affecting their accumulation.