To make use of oxidative metabolism as the most efficient means of metabolizing food, life forms have adapted to the toxicity of oxygen in a myriad of ways. Phosphorus, sulfur, selenium, and nitrogen can provide protection from reactive oxygen species and can also facilitate important cell signaling functions. The chemistries of sulfur (or selenium) allow for reversible oxidation/ reduction cycles that permit important control of cell functions. In addition, nitrogen and its oxides are ubiquitous in regulating many aspects of cell physiology. Phosphorus-based kinases and phosphatases regulate many pathways that control cell proliferation and gene regulation. Altered regulation of some of these pathways has been linked with various human diseases, including cancer and cardiovascular disorders and has provided an important platform for drug discovery and development.