The microscopic polymer mode-coupling theory is generalized to treat diffusion in unentangled and entangled homogeneous polymer blends. Concentration fluctuations are shown to result in additional frictional resistance to chain translation, due to physical clustering and nonrandom mixing effects. The modification of the pure component effective friction coefficient depends sensitively on polymer degree of polymerization, temperature, blend composition, solution density, and nonuniversal local structure. Stronger effects are predicted for entangled systems near a liquid-liquid phase boundary. Model calculations and analytic results are presented for self-diffusion in structurally symmetric binary mixtures. Our predictions are qualitatively consistent with existing experimental measurements. Based on the theory, new experiments are suggested for blends in which the influence of concentration fluctuations on measured diffusion constants is maximized.