This review considers advances in the understanding of active pharmaceutical ingredient polymorphism since around 2010 mainly from a structural view point, with a focus on twelve model drugs. New polymorphs of most of these drugs have been identified despite that the polymorphism of these old drugs has been extensively studied so far. In addition to the conventional modifications of preparative solvents, temperatures, and pressure, more strategic structure-based methods have successfully yielded new polymorphs. The development of analytical techniques, including X-ray analyses, spectroscopy, and microscopy has facilitated the identification of unknown crystal structures and also the discovery of new polymorphs. Computational simulations have played an important role in explaining and predicting the stability order of polymorphs. Furthermore, these make significant contributions to the design of new polymorphs by considering structure and energy. The new technologies and insights discussed in this review will contribute to the control of polymorphic forms, both during manufacture and in the drug formulation.