Covering: literature up to 2018 Terpenes are a class of natural products characterized by remarkable structural diversity. Much of this diversity arises biosynthetically from a handful of linear precursors through the so-called tail-to-head terpene cyclization reaction. This reaction is one of the most complex observed in nature, and historically attempts to replicate it with non-enzymatic means have met with little success. In recent years, however, the development of manmade binding pockets that allow such reactions to take place has been reported. This Highlight provides an overview of this nascent field, and outlines the challenges that need to be overcome moving forward.