This review is intended to provide the reader with an overview of the all-purpose topical insect repellent N,N-diethyl-3-methylbenzamide (deet), with emphasis on its pharmacokinetics, formulation, and safety aspects. N,N-diethyl-3-methylbenzamide is effective against a variety of mosquitoes, flies, fleas, and ticks, and its protection efficacy depends on factors such as type of formulation, application pattern, physical activity of the user, environment, and species and feeding behavior of the insects. It offers an inexpensive and practical means of preventing the attack of biting insects and, more importantly, the transmission of vector-borne diseases. In both humans and animals, deet skin penetration and biodistribution are rapid and extensive, and metabolism and elimination appear to be complete. As evidenced by over 4 decades of human experience and rigorous animal testing, deet is generally safe for topical use if applied as recommended, although it has occasionally been related to side effects such as toxic encephalopathy, seizure, acute manic psychosis, cardiovascular toxicity, and dermatitis, along with a few cases of death due to extensive skin absorption. N,N-diethyl-3-methylbenzamide may compete in metabolism with and alter the biodistribution properties of other compounds to which a subject is simultaneously exposed, resulting in an added risk of side effects. The appropriate use of formulation techniques and new formulation excipients not only offers a way to extend the duration of protection, but also reduces deet skin penetration. In addition to extended repellency, minimal skin penetration of deet should be an important consideration in the evaluation of a deet formulation during new product development.