Both computational and experimental results show that oxygen vacancies and polarons activate TiO2 towards HER. Hence, one can control the HER activity by tuning the oxygen vacancy concentration through different synthesis methods and by controlling polaron formation through electrode potential. The presence of polarons also depends on the presence of vacancies, and vice versa. Because the electrode potential controls both vacancy and polaron formation, which in turn control the overall electrocatalytic activitythese factors cannot be optimized independently. In photoelectrocatalytic applications one also needs to account for the light illumination and e.g. its impact of polaron formation. Computational methods can aid by providing information about the interplay between polarons and vacancies, but the calculations must explicitly consider the electrode potential effects because the polaron formation, electronic structure, surface charge, and reaction energetics depend non-trivially on the electrode potential (Figures ) For instance, we find that the linear free energy relationships between reaction energies and barriers as a function of potential do not hold for TiO2 in the region of potential-dependent polaron formation: this implies that polaron formation breaks (Figures ) the traditional Butler-Volmer-like linear relationship observed for HER on various metallic surfaces, see detailed discussion in Figure . Also, the number of electrons in the system varies non-linearly when the system proceeds from the initial (IS) to transition (TS) and to final states (FS) at a constant electrode potential, see Figure . This behavior is qualitatively different from that observed on metallic electrodes where the number of electrons exhibit monotonous linear increase as the reaction proceeds from IS to FS. Crucially, the broken linear-free energy relations and potential-dependent polaron/vacancy formation indicate that one should not extrapolate measurements at low over-potentials to infer electrocatalytic performance under the relevant reaction conditions.