The development of ultrasound backscatter microscopy (UBM) is described together with initial clinical and biological applications. UBM is essentially an extension of the powerful B-mode backscatter methods developed for clinical imaging in the 3-10-MHz frequency range. The development of new high sensitivity transducers in the 40-100-MHz range now permits visualization of tissue structures with resolution approaching 20 mum and a maximum penetration of approximately 4 mm. The performance characteristics and trade-offs of these new polymer and ceramic devices are reviewed, and the implementation of high-frequency imaging systems is described. Initial clinical applications of UBM include ophthalmic, skin, and intravascular imaging. Examples of images and progress in these areas are presented. The biological application of UBM is illustrated by studies of drug uptake in living tumor spheroids. Significant increases in backscatter levels resulting from drugs targeting oxic and hypoxic cell populations are demonstrated.