Structure–activity relationship and quantitative SAR are modeling methods largely used in assessing biological properties of chemical substances. QSAR is based on the hypothesis that the chemical structure is responsible for the activity; it follows that similar molecules are expected to have similar properties. Similarity plays an important role in read across, which categorizes molecules primarily on the basis of similarity. Similarity, and chemical similarity too, is a property differently perceived by humans. The various proposed metrics often disagree with human judgment, (...) and no a unique metric for chemical similarity is universally adopted. Researchers argued that categorization is not only explained by similarity but depends as well on abstract knowledge and the task to accomplish. Moreover, similarity cannot be the unique explanation of a categorization, as different perceptual processes take place in category formation. Assuming that similarity judgments are deeply rooted in human knowledge and perception, cognitive sciences contributions are as important as the mathematical considerations of the classical theories. After an excursus in the many views of similarity in philosophy, mathematics, and cognitive science, the paper explores how connectionist systems, which loosely mimic the human cognitive system, could improve similarity-based choices. A case study on building SARs using connectionism and deep neural networks shows the role of similarity in building and explaining those models. A discussion about deep learning for QSAR and as a modeling tool for science concludes the presentation. (shrink)