Polypeptide brushes are attractive platforms to generate functional and responsive interfaces that are of potential interest due to their possible biodegradability, biocompatibility and tunable secondary structures. Surface-initiated ringopening polymerization (SI-ROP) of alpha-amino acid N-carboxyanhydrides represents a powerful and versatile strategy to generate polypeptide brushes. This review is an attempt to capture the state-of-the-art in this field and highlights the latest developments in several selected areas. In addition to presenting an overview of the synthetic methods that have been used to generate polypeptide brushes via SI-ROP, this article will discuss the preparation of patterned polypeptide brushes, the conformational properties of surface-tethered polypeptides, ways to control chain orientation at surfaces as well as properties and applications of these thin polymer films.