This presentation offers a comprehensive, evidence-based review of feline histoplasmosis, the second most common systemic fungal disease in cats. This presentation shares diagnostic and treatment insights derived from over 400 suspected cases at a feline-only practice, emphasizing the growing incidence of disease and its diverse clinical manifestations. Attendees will gain practical knowledge on identifying at-risk cats, interpreting diagnostic tests—especially antigen testing—and implementing long-term antifungal therapy. The session also covers the unique challenges of managing advanced disease, treatment monitoring, and the importance of client education, nutrition, and environmental considerations for successful outcomes.