Orphan drug designation is a special status that sponsors can seek when developing a medicinal product to prevent, diagnose or treat a rare disease, a condition that affects a small number of patients. This designation confers significant incentives to sponsors, a strategic way to promote the development and marketing of drugs for rare conditions. Applications can be challenging since data is often scarce and studies usually deal with a heterogeneous population. With our experience, we will tackle these complexities and join forces not only in the application process but also in the maintenance of the subsequent periodic reports.