Computational tools have been developed over the past four decades to alleviate these issues and help the synthetic chemist (and/or their CADD colleague) find a viable synthetic route for a novel molecule. They can be broadly categorized into two classes: synthesizability estimation ; and synthetic route prediction (variously called computer assisted synthesis design (CASD), computer-assisted organic synthesis (CAOS), computer-assisted synthesis planning (CASP), computer-assisted reaction design (CARD), and yet other terms) . While the former is often based on statistical, QSAR-like approaches and used (only) in the context of in silico screening, the latter typically apply some kind of retrosynthetic reasoning and were meant to support the bench chemist. These tools had their heyday during the 1980s and 1990s but subsequently fell out of favor as an approach used in practice, and the entire field went essentially dormant. Several reasons can be proffered for this, including: If the program selected one out of the typically very large number of possible routes, the proposed route was often either found not to work (well) in practice, or was rejected as unrealistic right away based on the chemist's experience; if, conversely, the software presented the user with a tree of possibilities, the amount of work to analyze these hundreds or thousands of possible routes was deemed unacceptable; hardware capabilities were insufficient to implement these approaches to their fullest potential and with enough speed; the programs were difficult to use including less user-friendly (or no) GUIs; the number of commercially available building blocks was much smaller than nowadays; advances in synthetic methods made existing knowledge bases obsolete; and perhaps the psychological issues of fearing these approaches might lead to replacement of human experts with machines.