To enhance the attrition rate of drug candidates a rapid identification and elimination of compounds with unsuitable pharmacokinetic properties are needed. In this context physicochemical and permeation profiling of new chemical entities (NCEs) can be very helpful in terms of early high-throughput screening (HTS) filters. A complex panel of methods is available to predict or measure physicochemical properties. However the lack of quality of existing filters often produces some troubles in the drug development process by keeping drug candidates with a poor pharmacokinetic profile or by eliminating adequate NCEs. This presentation will focus on recent experimental advances dealing with key properties such as ionization, solubility, lipophilicity, and membrane permeation.