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Almost 2 decades ago, it was pointed out that physical therapists tended to overlook the tenuous nature of the scientific basis for the use of therapeutic ultrasound. The purpose of this review is to examine the literature regarding the biophysical effects of therapeutic ultrasound to determine whether these effects may be considered sufficient to provide a reason (biological rationale) for the use of insonation for the treatment of people with pain and soft tissue injury. This review does not discuss articles that examined the clinical usefulness of ultrasound (see article by Robertson and Baker titled “A Review of Therapeutic Ultrasound: Effectiveness Studies” in this issue). The frequently described biophysical effects of ultrasound either do not occur in vivo under therapeutic conditions or have not been proven to have a clinical effect under these conditions. This review reveals that there is currently insufficient biophysical evidence to provide a scientific foundation for the clinical use of therapeutic ultrasound for the treatment of people with pain and soft tissue injury.