The main roles of DNA in the cells are to maintain and properly express genetic information. Damage to DNA in the cells, upon interactions with a number of chemical and physical agents occurring in the environment, often results in mutations that may subsequently lead to cancer development. It is therefore important to have analytical methods capable of fast and sensitive detection of both DNA damage and DNA damaging agents. Electrochemical analysis of DNA offers a number of approaches in DNA damage detection as well as in sensing of DNA damaging agents in the environment, in food in clinical samples, etc. These approaches include a) measurements of faradaic and tensammetric intrinsic DNA signals at mercury or solid electrodes, and b) utilization of the signals of electroactive substances interacting with DNA covalently or non-covalently. A simple electrochemical sensor for DNA damage consists of an electrode (signal transducer) and DNA immobilized on the surface of the former (recognition layer). Interactions of the surface-confined DNA with a DNA damaging agent are converted, via changes in electrochemical properties of the DNA recognition layer into measurable electrical signals. This review is devoted to electrochemical studies of damaged DNA and of DNA interactions with small molecules, and to up-to-date progress in the field of DNA electrochemical sensors for DNA damaging substances, including genotoxic agents such as carcinogens and mutagens, or clinically used drugs.