The sense of taste is defined as a part of the sensory system in which taste receptors are able to detect a variety of chemical molecules and provide valuable information allowing the discrimination of five basic tastes: sweet, sour, salty, umami, and bitter. Humans have about 25 different receptors for bitter taste that belong to the G-protein-coupled receptor superfamily. They can detect at least 1000 chemicals and herbal compounds. Among these, many active pharmaceutical ingredients (API) are characterized by an unpleasant taste that hinders patients’ willingness to take their medicinal products. Based on the FDA draft guidelines, palatability has been defined as “the quality of a pharmaceutical product that makes it agreeable or acceptable in taste, aftertaste, odor and texture.” It is therefore essential during the development of a pediatric drug to evaluate whether an adverse taste is expected, as well as the mouthfeel, in order to ensure formulation palatability. This chapter focuses on the mechanisms of interaction between the API, the galenic forms, and all the orosensory receptors and provides a comprehensive overview of the state-of-the-art research on palatability of oral dosage forms. Moreover, an overview is given about available in vivo test methods in order to present the meaning of evaluating sensory perception. These are the Human Taste Panel, Sip and Spit Studies, and the BATA model (Brief-access taste aversion). For the in vitro tools, e-tongue model and cell-based model are shown. Less common methods such as amoeba-based assessment or methods using zebrafishes are also discussed. An additional part will discuss the options of in silico modeling of taste.