Acute respiratory infections are responsible for an estimated 4 million deaths annually worldwide, and are the leading cause of death in children younger than 5 years. Over 1 million people in the United States are hospitalized each year with pneumonia. Mycobacterium tuberculosis infects one third of world’s population. There are more than 1 million tuberculosis-related deaths worldwide each year. Emerging resistance to multiple available antimicrobial agents has hampered the ability to treat tuberculosis and hospital-acquired respiratory infections. The laboratory diagnosis of respiratory infections is an important part of patient management and treatment. In addition to culture isolation of pathogens, advances have been made in a number of non-culture methods. This issue of Clinics in Laboratory Medicinee reviews state-of-the-art laboratory diagnosis of respiratory infections, as well as the testing of susceptibility to antibiotics and antiviral agents. Among some of the respiratory infections covered are: Cystic fibrosis infections; Pertussis; Pharyngitis; Fungal infections. Among the diagnostic tests are: Interferon gamma release assays; Molecuar diagnosis of TB; Urine antigen tests and discussion of Antibiotic resistance in nosocomial respiratory infections.