AbstractDifferent polymorphs of the same active pharmaceutical ingredient (API) display distinct physical properties, such as melting point, solubility, dissolution rate, hygroscopicity, or stability. The ability to successfully produce and reproduce specific stable polymorphs is intricately correlated with the efficiency and speed of drug development, the robustness of manufacturing process, and – ultimately – the stability and quality of APIs. This paper focuses on eight case study examples of interesting polymorphic transformations observed in the course of the regular API development process. Through extensive physicochemical characterization, using multiple analytical techniques, the phenomena observed could be elucidated and proper measures recommended to reduce the risk of unexpected polymorphic transformations.