Medical biotechnology has experienced rapid growth, driven by the increasing demand for biologicals, including biological medicines, vaccines, and advanced therapy medicinal products (ATMPs) based on genes, cells, or tissues. Pharmaceutical biotechnology companies are actively developing therapies to address unmet medical needs across a range of diseases, including cancer, autoimmune, cardiovascular, dermatological, metabolic, and neurological disorders. Biological medicines and ATMPs are regulated by the European Medicines Agency (EMA) in Europe and the Food and Drug Administration (FDA) in the USA, with both agencies offering similar definitions for biosimilars. However, the formulation of biologicals presents challenges, particularly regarding stability and overcoming biological barriers due to their molecular characteristics, such as large size and hydrophilicity. These medicines are typically administered via parenteral injections, which have drawbacks like pain, invasiveness, and high production costs. Researchers have been exploring alternative routes of administration for biologicals, including the nasal route, and in particular the nose-to-brain route, which shows promise for molecules targeting the brain avoiding the need to cross the blood-brain barrier (BBB). It is therefore surprising that, to the best of our knowledge, no biological product has been approved specifically for the nose-to-brain route and only a few nasal biological vaccines have been approved by the EMA and the FDA. This shows that this is an open area for future research and development. This chapter describes the characteristics of the nose-to-brain route and provides an overview of its current applications in promoting the delivery of biologicals to the brain.