Translational Science demands the integration of all the biomedical sciences to optimise delivery of the objective of any drug discovery project: demonstration of an effect of new medical entities in patients. This chapter will address some key established practises that should be included in any compound screening cascade from target protein through to clinical utility, enabling evidence based progression of a compound into human testing and ensuring the likelihood of demonstrating an effect. It is intended to give an indication of the challenges that should be considered when establishing a screening cascade and the suitability of different assays for defined purposes. This chapter should aid any new project team member in understanding the reasons for the tests that are being applied and allow them to contribute to the ongoing discussions and development of the project strategy. We highlight where the role of the medicinal chemist is critical to addressing many of the biological challenges that occur in attempting to validate a target and demonstrate clinical utility suitable for regulatory acceptance.