Historically, dope-testing methods have been developed to target specific and known threats to the integrity of sport. Traditionally, the source of new analytical targets for which testing was required were derived almost exclusively from the pharmaceutical industry. More recently, the emergence of designer drugs, such as tetrahydrogestrinone that are specifically intended to evade detection, or novel chemicals intended to circumvent laws controlling the sale and distribution of recreational drugs, such as anabolic steroids, stimulants and cannabinoids, have become a significant issue. In this review, we shall consider the emergence of designer drugs and the response of dope-testing laboratories to these new threats, in particular developments in analytical methods, instrumentation and research intended to detect their abuse, and we consider the likely future impact of these approaches.