Cryptococcus is among the most common invasive fungal pathogens globally and is one of the leading causes of acquired immunodeficiency virus-related deaths. Cryptococcus neoformans and Cryptococcus gattii are the most clinically relevant species and account for most cryptococcal disease. Pulmonary manifestations can range from mild symptoms to life-threatening infection. Treatment is tailored based on the severity of pulmonary infection, the presence of disseminated or central nervous system disease, and patient immune status. Amphotericin B and flucytosine followed by fluconazole remain the standard agents for the treatment of severe cryptococcal infection.