The challenge remains to find the proper combination of these techniques in view of their respective potential, limitations, and costs, in order to pick up the right compounds quickly while keeping the risk of eliminating ‘good’ candidates as low as possible. Potential and limitations of a number of approaches to get early information on solubility and permeability, the main factors governing absorption via passive diffusion, will be discussed with practical examples.It aims at offering longlasting knowledge and stimulating food for thought. This is why its three main parts (biological, physicochemical, and computational strategies) are accompanied by two chapters which set the scene, four others which review the molecular and biological background of pharmacokinetic lead optimization, and finally two which conclude the book.