The interest and research effort into the development of DNA diagnostic tools has increased dramatically and new instruments to detect, analyze, and quantify gene‐specific information are expected to revolutionize healthcare. In this chapter, a number of application fields for DNA‐based biosensors are described, together with some examples highlighting the specific nature of DNA‐based diagnostics, its impact on biosensor requirements, and how specific challenges in the field can be addressed. An overview, illustrated with some original work, provides aspects of a potential route toward affordable DNA‐sensor arrays with a particular focus on multiplexing and compatibility with polymer integration technology.