Percutaneous imaging-guided needle biopsy has increasingly become an alternative to surgical biopsy for the histologic assessment of breast lesions. Percutaneous biopsy is faster, less invasive, and less expensive than surgical biopsy. Tissue acquisition is performed with automated core needles or directional vacuum-assisted biopsy probes. Guidance for percutaneous biopsy is usually provided by stereotaxis, ultrasound, and, more recently, under the guidance of MR imaging. Imaging guidance depends on lesion type and the results of diagnostic imaging studies. This article reviews indications, advantages, limitations, and controversial issues in percutaneous imaging-guided biopsy of breast lesions under stereotactic and ultrasound guidance. The potential for new research opportunities and directions is also discussed.