Animal model plays an important role in prevention and control of infectious disease, which could link basic research in laboratory with clinical diagnosis and treatment for human patients. Mouse is the most widely used animal model of infectious disease, however, adult immunocompetent mice are resistant to some pathogens. The highly genetically diverse Collaborative Cross (CC) mice could recapitulate many of the genetic characteristics of an outbred population, such as humans. Based on this, this review will focus on the application and research progress of CC mice in infectious disease (including viruses, bacteria, fungi etc.), which could provide useful reference data for expansion of animal model resource bank, and implement of precision medicine of major and new emerging infectious diseases. We hope this review could serve as a modest spur to induce other researchers to come forward with their valuable contributions.