Mouse models have been instrumental in understanding human disease biology and proposing possible new treatments. The precise control of the environment and genetic composition of mice allows more rigorous observations, but limits the generalizability and translatability of the results into human applications. In the era of precision medicine, strategies using mouse models have to be revisited to effectively emulate human populations. Systems genetics is one promising paradigm that may promote the transition to novel precision medicine strategies. Here, we review the state-of-the-art resources and discuss how mouse systems genetics helps to understand human diseases and to advance the development of precision medicine, with an emphasis on the existing resources and strategies.