The respiratory tract is a common site of infection in cancer patients and is associated with substantial moribidity and mortality in this population. Cancer, chemotherapy, and radiation can all cause noninfectious pulmonary infiltrates and respiratory symptoms that can masquerade as a respiratory tract infection. Cancer patients are at a particular risk for infection by a wide variety of different viruses, fungi, and bacteria that can be difficult to treat. Although noninvasive diagnostics have significantly improved recently, patients with severe pneumonia and those not responding to usual therapy should be candidates for aggressive diagnostic testing and tissue sampling. Initial therapy should be carefully chosen and individually tailored to account for the individual patient's underlying risk factors for multi-drug-resistant pathogens, viral pathogens, or fungi. Once diagnostic testing returns, therapy should be altered to appropriately narrow the spectrum of coverage.