The orthogonal subcategory problem in homotopy theory

It is known that the existence of localization with respect to an arbitrary (possibly proper) class of maps in the category of simplicial sets is implied by a large-cardinal axiom called Vopenka's principle.In this article we extend the validity of this result to any left proper, combinatorial, simplicial model category $\cat M$ and show that, under additional assumptions on $\cat M$, every homotopy idempotent functor is in fact a localization with respect to some set of maps. These results are valid for the homotopy category of spectra, among other applications.