Microorganisms are ubiquitous in subsurface environments and play a major role in the biogeochemical recycling of various elements. In this paper, we have developed a general approach for a systematic evaluation of microbial impact on the long-term performance of the repository. We have demonstrated that data on microbial population alone are not sufficient for the evaluation of microbial impact on repository performance and a sensible approach for such evaluation must be based on the consideration of environmental constraints on microbial reaction pathways. We have applied our approach to both the Yucca Mountain (YM) repository and the Waste Isolation Pilot Plant (WIPP). We have demonstrated that the effect of microbial activity on the near-field chemistry in the Yucca Mountain repository is negligible because of limited nutrient supply and harsh environmental conditions created by waste emplacement. Whereas for the WIPP, we have shown that, due to the presence of a large quantity of organic materials and nutrients in the wastes, a significant microbial activity can potentially be stimulated and its impact on repository performance can be evaluated with carefully designed incubation experiments coupled with performance assessment calculations. The impact of microbial gas generation on disposal room chemistry in the WIPP can be mitigated by introducing MgO as a backfill material.