Image-guided biopsy is a safe and well-established technique that is familiar to most interventional radiologists. Improvements in image guidance, biopsy tools, and biopsy techniques now routinely allow for safe biopsy of renal and adrenal lesions that traditionally were considered difficult to reach or technically challenging. Image-guided biopsy is used to establish the definitive tissue diagnosis in adrenal mass lesions that cannot be fully characterized with imaging or laboratory tests alone. It is also used to establish definitive diagnosis in some cases of renal parenchymal disease and has an expanding role in diagnosis and characterization of renal masses before treatment. Although basic principles and techniques for image-guided needle biopsy are similar regardless of organ, this paper highlights some technical considerations, indications, and complications that are unique to the adrenal gland and kidney because of their anatomic location and physiological features.