Resistance to antimicrobials is one of the biggest threats to our healthcare. However, in the last few decades very few truly novel antimicrobial compounds have been brought to market, creating the potential threat of a post-antibiotic era in which infections are very difficult to treat. Identification of novel compounds with antimicrobial activity is therefore paramount. Ideally, novel compounds should be designed that are active against targets that are not or barely used, as it is less likely that resistance already exists against such compounds. One example of an underexplored target in the treatment of infections is DNA. In this review we describe a number of DNA binding compounds and discuss potential opportunities and problems.