Preview The approach to immunocompromised patients with diffuse pulmonary infiltrates has become increasingly complex with the evolution of more intense immunosuppressive therapy. Controversy still exists regarding the use of invasive diagnostic procedures rather than empirical therapy for this heterogeneous group. Dr Staszewski explains the reasons for the uncertainty and recommends an individualized approach that takes into account type of immunosuppression, local resources, physician experience, and patient prognosis.