One of the drawbacks of conventional grand unification scenarios has been that the unification scale is too high to permit direct exploration. In this paper, we show that the unification scale can be significantly lowered (perhaps even to the TeV scale) through the appearance of extra space-time dimensions. Such extra dimensions are a natural consequence of string theories with large-radius compactifications. We show that extra space-time dimensions naturally lead to gauge coupling unification at intermediate mass scales, and moreover may provide a natural mechanism for explaining the fermion mass hierarchy by permitting the fermion masses to evolve with a power-law dependence on the mass scale. We also show that proton-decay constraints may be satisfied in our scenario due to the higher-dimensional cancellation of proton-decay amplitudes to all orders in perturbation theory. Finally, we extend these results by considering theories without supersymmetry; experimental collider signatures; and embeddings into string theory. The latter also enables us to develop several novel methods of explaining the fermion mass hierarchy via D-branes. Our results therefore suggest a new approach towards understanding the physics of grand unification as well as the phenomenology of large-radius string compactifications.