Quinones are a group of highly reactive organic chemical species that interact with biological systems to promote inflammatory, anti-inflammatory, and anticancer actions and to induce toxicities. This review describes the chemistry, biochemistry, and cellular effects of 1,2- and 1,4-naphthoquinones and their derivatives. The naphthoquinones are of particular interest because of their prevalence as natural products and as environmental chemicals, present in the atmosphere as products of fuel and tobacco combustion. 1,2- and 1,4-naphthoquinones are also toxic metabolites of naphthalene, the major polynuclear aromatic hydrocarbon present in ambient air. Quinones exert their actions through two reactions: as prooxidants, reducing oxygen to reactive oxygen species; and as electrophiles, forming covalent bonds with tissue nucleophiles. The targets for these reactions include regulatory proteins such as protein tyrosine phosphatases; Kelch-like ECH-associated protein 1, the regulatory protein for NF-E2-related factor 2; and the glycolysis enzyme glyceraldehyde-3-phosphate dehydrogenase. Through their actions on regulatory proteins, quinones affect various cell signaling pathways that promote and protect against inflammatory responses and cell damage. These actions vary with the specific quinone and its concentration. Effects of exposure to naphthoquinones as environmental chemicals can vary with the physical state, i.e., whether the quinone is particle bound or is in the vapor state. The exacerbation of pulmonary diseases by air pollutants can, in part, be attributed to quinone action.