Over the last years, there has been an exponentially growing need and interest to bring pharmacokinetic expertise into discovery. In order to allow a multidisciplinary selection and a higher attrition rate, both the in vivo and in vitro pharmacokinetic parameters of an ever increasing number of tentative new chemical entities are evaluated in an earlier phase of Drug Discovery. A higher attrition rate at the beginning of the pipeline should result in a lower attrition rate at a later stage in development. In this process, the bioanalytical laboratory has become increasingly important. Analytical strategies needed to be adapted to cope with novel experimental designs such as cassette dosing, cassette analysis or 96-well techniques. At the same time, HT-synthesis programs surfaced a broader variety of chemical classes to be investigated, disfavoring further generalization of analytical approaches. Progress in lab automation, improved chromatographic techniques and the proliferation of LC-MS/MS enabled the analyst to deal with these challenges much faster and with a higher level of confidence. Quality standards regarding method development and method validation, setting the boundaries for more than a decade, needed to be titrated to reach an optimal balance between speed and quality. This review will give an illustrative overview of the bioanalytical techniques and strategies used to support Drug Discovery, together with some pitfalls related to the overzealous use of new techniques.