Olfactory dysfunctions (OD) affect nearly 20% of the world’s population, which has a major impact on their quality of life. Several treatment options exist, but so far, no olfactory prosthesis has been invented to help people with OD. This chapter presents a proof of concept for an olfactory prosthesis in which a substitution sense is used to replace the sense of smell. This sense, the trigeminal sense, provides hot/cold and tickling or even tingling intranasal sensations. The chapter is based on a study published in the context of a European interdisciplinary consortium (Rose project). The proof of concept consists of an odorant molecule sensor and an intranasal stimulator. Results showed that patients were able to detect the presence of an odor via the trigeminal substitution signal and the majority of them were able to distinguish between two intranasal stimulations. These results represent an important step toward a proof of concept for an olfactory substitution prosthesis.