The replacement of aromatic rings with saturated molecular frameworks is a recent development encapsulated by the motto "escape from flatland" and conceptualized through the use of saturated benzene bioisosteres. This Review summarizes the application of the smallest bicyclic and spirocyclic ring systems as saturated scaffolds, focusing on applications in constructing bioactive molecules. We discuss considerations of their molecular strains, their potential to serve as saturated benzene isostere