Discovery pharmacokinetics has moved a long way from starting off as service function which served to improve basic PK parameters such as clearance, half-life and bioavailability in potency-optimised compounds in response to the excessively high attrition of 40% due to poor pharmacokinetic properties of drug candidates during clinical testing in the 1980s and early 1990s. Even in its rather service-oriented role, the impact of addressing ADME issues from early on in drug discovery programmes was astonishing, reducing PK-related failure rates down to 10% in about a decade. The impressive effect has owned discovery DMPK not only fullacceptance; it is now seen at the core of drug discovery being an integral part of every drug discovery project.Although, today, we are still a long way from understanding and translating cellular effects to pharmacodynamic and safety-related effects in tissues and further to clinical readouts, the exposure-based PK support is a powerful approach that helps advancing. the discovery, optimisation, selection and characterisation of high-quality drug candidates with PK/PD properties