Prognostic models are developed to be applied in new patients, who may come from different centres, countries, or times. Hence, new patients are commonly referred to as different from but similar to the patients used to develop the models.1 2 3 4 But what exactly does this mean? When can a new patient population be considered similar (enough) to the development population to justify validation and eventually application of a model? We have already considered the design, development, and validation of prognostic research and models.5 6 7 In the final article of our series, we discuss common limitations to the application and generalisation of prognostic models and what evidence beyond validation is needed before practitioners can confidently apply a model to their patients. These issues also apply to prediction models with a diagnostic outcome (presence of a disease).