Microbial responses to climate change will partly control the balance of soil carbon storage and loss under future temperature and precipitation conditions. We propose four classes of response mechanisms that can allow for a more general understanding of microbial climate responses. We further explore how a subset of these mechanisms results in microbial responses to climate change using simulation modeling. Specifically, we incorporate soil moisture sensitivity into two current enzyme-driven models of soil carbon cycling and find that moisture has large effects on predictions for soil carbon and microbial pools. Empirical efforts to distinguish among response mechanisms will facilitate our ability to further develop models with improved accuracy.