We study quark flavor violating interactions mediated by the Higgs boson h. We consider observables involving a third generation quark, of both the up and the down quark sectors, like h → bs and t → ch. Using an effective field theory approach we systematically list all the possible tree-level ultraviolet completions, which comprise models with vector-like quarks and/or extra scalars. We provide upper bounds on the flavor violating transitions allowed by current limits stemming from low energy processes, such as meson mixing and b → sγ. We find that scenarios with vector-like quarks always have very suppressed flavor-violating transitions, while a general two Higgs doublet model may have a sizeable rate. To study the latter case in detail, we perform a full numerical simulation taking into account all relevant theoretical and phenomenological constraints. Our results show that BR(t → ch) [BR(h → bs)] are still allowed at the subpercent [percent] level, which are being [may be] explored at the LHC [future colliders]. Finally, we have found that the mild mass-splitting discrepancy with respect to the SM in the B s meson system can be accommodated in the Two-Higgs-Doublet Model. If confirmed, it yields the prediction BR(h → bs) 10 −4 , if the new contribution to the mass-splitting is dominated by tree-level Higgs boson exchange.