Single-step retrosynthesis frameworks can be classified into three major categories: i) Template-based, ii) Template-free, and iii) Semi-template frameworks. Figure provides a visual abstraction of each category. Generally, the differences between categories boil down to the inclusion or exclusion of reaction templates. Figure shows an example of a reaction template. One can compare a reaction template to a rule, which provides information about bond formation and breakage in the reaction centre. Formally, a reaction centre is defined as the atoms and bonds that participate in electron rearrangement during the reaction . Frameworks that employ templates to perform chemical retrosynthesis belong to the template-based category. Since templates are either manually curated or automatically extracted from existing literature , they inherently distil chemical (expert) knowledge within the model. On the other hand, models can learn from reaction data directly without the use of pre-defined rules in the form of templates. These models belong to the template-free category as shown in Figure . Finally, semi-template models are data-driven models that necessitate information from reaction templates for the purpose of training the model (but not during inference). This information is provided in the form of atom mapping. Atom mapping can be seen as a dictionary, that for each atom in the reactants, defines the matching atom in the product (target) molecules. Since reaction templates are curated from atom mapping, semi-template and template-based models share a certain degree of knowledge, thus giving rise to the naming convention.