Ultrasound energy exerts important cellular, genetic, thermal, and mechanical effects. Concern about the safety of ultrasound prompted several agencies to devise regulatory limits on the machine output intensities. The visual display of thermal and mechanical indices during ultrasound imaging provides an aid to limit the output of the machine. Despite many animal studies, no human investigations conducted to date have documented major physiologic consequences of ultrasound exposed during imaging. To date, ultrasound imaging appears to be safe for use in regional anesthesia and pain medicine interventions, and adherence to limiting the output of ultrasound machines as outlined by the Food and Drug Administration may avoid complications in the future. This article reviews ultrasound-related biologic effects, the role of the regulatory agencies in ensuring safety with the use of ultrasound, and the limitations and implications of ultrasound use in humans.