Highly potent neutralizing nanobodies (Nbs) are of great interest as potential COVID-19 therapeutics. Here, the authors show that potent neutralizing Nbs targeting the receptor binding ___domain (RBD) of the SARS-CoV-2 spike protein are also effective against convergent variants of concern of the virus. They determine eight Nb-bound spike protein cryo-EM structures, classify the binding epitopes of the Nbs and discuss their neutralization mechanisms.