Natural fertilizers such as manure have historically been used to increase land productivity. However, it was not until the 19th century, when chemistry came to the forefront as a discipline, that the essential ingredients that conferred this productivity were discovered. Now, modern fertilizers containing the three elements found to be essential to plant nutrition (nitrogen, phosphorus, and potassium [NPK]) are easily available for general use. This is because chemists, over the course of the past 15 decades, have applied their knowledge to producing fertilizers economically on an industrial scale. Increased food output facilitated by fertilizers has contributed to exponential population growth, accompanied by an increasing concern for the environmental impact of overfertilization. Other issues include best practices for managing fertilizer application and risk assessment of their use. Thus, a great challenge of the 21st century will be to manage the benefits as well as the negative consequences of fertilizers to assure a sufficient food supply and protect the environment. This chapter addresses these concerns.