Ultrasound (US)-guided transthoracic biopsy is well suited for the sampling of those mediastinal, hilar, pleural, chest-wall, and peripheral lung lesions that provide an adequate acoustic window to the transducer. Chest-wall, pleural, and peripheral lung lesions are generally hypoechoic relative to their surrounding tissues. A special puncture transducer is used to perform US-guided biopsy with real-time visualization of the biopsy needle and the lesion. For vascular lesions and lesions adjacent to mediastinal vessels, a color Doppler puncture device is now available. The accuracy of US-guided biopsy of peripheral lung lesions or chest-wall lesions is 88% to 100%, with particular utility in the diagnosis of pulmonary masses with large necrotic centers. Other lung lesions amenable to US-guided biopsy diagnosis include those producing superior vena cava (SVC) syndrome, Pancoast's syndrome, or obstructive pneumonitis. Pulmonary consolidation, lung abscess, and parapneumonic effusions are easily sampled for microbiologic diagnosis. The peripheral nature of lesions accessed by US guidance accounts for a very low rate of complications. Although US-guided needle biopsy requires certain expertise, the technique is relatively easy to master and can be performed in many situations where computed tomography-guided biopsy would previously have been used.