Systemic fungal diseases cause significant morbidity and mortality in dogs and cats. Blastomycosis, histoplasmosis, coccidiomycosis, and cryptococcosis represent the four most common systemic fungal diseases. Young adult, large breed dogs generally are predisposed; cats usually do not have predictable predispositions. Intact cell-mediated immunity is essential to initial resistance to infection and response to treatment in animals. Several body systems can be affected. Diagnosis can be confirmed on the basis of clinical signs and demonstration of the causative organism. Serology is helpful with coccidiomycosis and cryptococcosis. Treatment is complicated by limited availability of fungicidal antimicrobials and the necessity of long-term treatment with expensive drugs.