This article describes the chemical nature of α,β-unsaturated aldehydes and some of their toxicological effects based on their ability to function as direct-acting alkylating agents. Selected compounds discussed include α,β-unsaturated aldehydic environmental pollutants, metabolites of xenobiotics and natural products, and lipid peroxidation—and DNA oxidation products derived from cellular constituents. Briefly reviewed are sources and mechanisms of formation of the aldehydes, their reactivity with respect to glutathione and amino-groups, their toxicity based on interaction with sulfhydryl and amino targets in cells, and modulation of their toxicity by metabolism.