The interpretable properties of a molecular are some of the most important and commonly used in drug discovery. Simple rules can be defined that reflect trends in the druglike box where drugs tend to sit, although many drugs fall outside this historically defined box. Many different properties have been defined and correlations drawn between those properties and important biological endpoints. However, the physicochemical properties are only surrogates and should be used with caution in this aspect. That said, however, many properties are useful guide points and can be applied usefully, particularly when not being applied overly stringently. This chapter covers a number of commonly applied physicochemical descriptors and their method of calculation. Consideration is given to their application in the drug design process and how they are applied to benefit these programmes.