Today, solid-state properties of Active Pharmaceutical Ingredients (APIs) play an important role in pharmaceutical research and development as it has a key impact on parameters such as bioavailability, manufacturability and stability. This was not always the case. Much awareness for this topic has been caused by the so called “Ritonavir” case, which almost ended up in a disaster for one of the first anti-HIV drugs in the early 90th. Since then much scientific knowledge has been obtained and solid-state form screening, selection and development has been introduced in a systematic way in pharmaceutical research and development. Despite of this, still today unexpected things happen which can be challenging. The lecture will provide an overview of how this systematic approach has developed and also show unexpected surprises.