The existence of a new physical form of a drug substance with a bioavailability significantly different from that of the original form can have serious effects on the therapeutic levels of the dosage form. The goal of any dosage form is to ensure reproducible safe exposure during preclinical and clinical studies, and ultimately for the marketed product. This review discusses the different physical forms of a drug substance, including amorphous forms, polymorphs, hydrates and salts, and the importance of characterizing the form of the drug substance during development. A definition of the different forms is provided, and enantiotropism, monotropism and polyamorphicity are discussed. This article provides examples of cases in which changes in the physical form resulted in changes in stability and/or bioavailability of the product. The review also discusses some of the methods used to quantify the physical form of a drug substance in a product.