We consider the two-Higgs-doublet model as a framework in which to evaluate the viability of scenarios in which the sign of the coupling of the observed Higgs boson to down-type fermions (in particular, b-quark pairs) is opposite to that of the Standard Model (SM), while at the same time all other tree-level couplings are close to the SM values. We show that, whereas such a scenario is consistent with current LHC observations, both future running at the LHC and a future e +e − linear collider could determine the sign of the Higgs coupling to b-quark pairs. Discrimination is possible for two reasons. First, the interference between the b-quark and the t-quark loop contributions to the ggh coupling changes sign. Second, the charged-Higgs loop contribution to the γγh coupling is large and fairly constant up to the largest charged-Higgs mass allowed by tree-level unitarity bounds when the b-quark Yukawa coupling has the opposite sign from that of the SM (the change in sign of the interference terms between the b-quark loop and the W and t loops having negligible impact).