Physiology of the human body in space has been a major concern for space-faring nations since the beginning of the space era. Ultrasound (US) is one of the most cost effective and versatile forms of medical imaging. As such, its use in characterizing microgravity-induced changes in physiology is being realized. In addition to the use of US in related ground-based studies, equipment has also been modified to fly in space. This involves alteration to handle the stresses of launch and different power and cooling requirements. Study protocols also have been altered to accommodate the microgravity environment. Ultrasound studies to date have shown a pattern of adaptation to microgravity that includes changes in cardiac chamber sizes and vertebral spacing. Ultrasound has been and will continue to be an important component in the investigation of physiological and, possibly, pathologic changes occurring in space or as a result of spaceflight.