RUVBL1 and RUVBL2 are two highly conserved AAA+ ATPases that form a hetero-hexameric complex that participates in a wide range of unrelated cellular processes, including chromatin remodeling, Fanconi Anemia (FA), nonsense-mediated mRNA decay (NMD), and assembly and maturation of several large macromolecular complexes such as RNA polymerases, the box C/D small nucleolar ribonucleoprotein (snoRNP) and mTOR complexes. How the RUVBL1-RUVBL2 complex works in such a variety of processes, sometimes antagonistic, has been obscure for a long time. Recent cryo-electron microscopy (cryo-EM) studies have started to reveal how RUVBL1-RUVBL2 forms a scaffold for complex protein-protein interactions and how the structure and ATPase activity of RUVBL1-RUVBL2 can be affected and regulated by the interaction with clients.