The growing importance of infectious caused by Aspergillus species during the last decade has created a need for practical and reproducible animal models of invasive aspergillosis suitable for studying fungal virulence, infection pathogenesis, diagnostic markers, and testing of antifungal therapy. Murine models remain the most commonly used models for studying aspergillosis because of their ease of manipulation and the large number of reagents available for studying disease-host responses. This chapter provides describes a murine model of invasive aspergillosis suitable for basic and translational studies of invasive pulmonary aspergillosis and highlights experimental variables that affect the course and reproducibility of infection.