© 2015, Hacettepe University, Faculty of Pharmacy. All rights reserved.Endogenous and exogenous factors can cause different types of DNA damages. The most dangerous DNA damage is double strand break (DSB). Under normal conditions, DSB repair is substantiated by two different mech- anisms. However, any disruption in these repair pathways can cause cancer, aging and different types of genetic disorders. Reactive oxygen species (ROS) induced by physical, chemical and biological agents are the main causes that lead to the formation of DSBs. In living tissues, ionized radiation can in- teract with water molecules and can cause oxidative stress and formation of ROS and DSB, respectively. Several chemical agents or drugs that humans are exposed to, by environment or therapy (anticancer drugs, heavy metals, asbestos, phthalates, benzene, ochratoxin A), were shown to cause DSB by several studies. Research on DSB causing effects of Helicobacter pylori, a bacterium that causes gastritis and ulcer in humans, is still in progress. In addition, several bacterial toxins were stated to cause DSB. This review will mainly focus on agents that cause DSB and their mechanisms of action.