Accessibility, of which synthesizability is an important part, differs vastly between chemical spaces (Figure ). Theoretically, we could generate a very large chemical space of molecules by enumerating all possible combinations of atoms and bonds, subject only to valency constraints. However, most of them would not be synthesizable or even stable, let alone reasonable. In contrast, the molecules in a high-throughput screening (HTS) deck are highly accessible because the compounds are already on stock, and do not have to be made on demand. Virtual molecules, generated on the fly with synthesizability constraints, represent a trade off, as they can often be readily obtained, while at the same time cover large chemical spaces.