We study twisted vector bundles of infinite rank on gerbes, giving a new point of view on Grothendieck’s famous problem on the equality of the Brauer group and cohomological Brauer group. We show that the relaxed version of the question has an affirmative answer in many, but not all, cases, including for any algebraic space with the resolution property and any algebraic space obtained by pinching two closed subschemes of a projective scheme.We also discuss some possible theories of infinite rank Azumaya algebras, consider a new class of “very positive” infinite rank vector bundles on projective varieties, and show that an infinite rank vector bundle on a curve in a surface can be lifted to the surface away from finitely many points.