Astonishing progress has been achieved in unlocking new-to-nature biocatalysis in the past decades. The progress in protein engineering enabled research to efficiently incorporate artificial structural elements into enzyme design. Recent trends include cofactor mimetics, artificial metalloenzymes and non-canonical amino acids. In this perspective article, we present the state-of-the-art, discuss recent examples and our view on what we call artificial biocatalysis. Although these artificial systems undoubtedly increase the scope of biocatalysis, their applicability remains challenging. Fundamental questions regarding the impact of this research field are addressed in this perspective.