There has been an increase in the use of ultrasound (US) to help guide interventional procedures involving the musculoskeletal system. To perform these procedures safely and accurately, two steps must occur. First, the appropriate structure must be localized using diagnostic US imaging. Second, a needle must be guided under constant visualization toward the targeted tissue. Although US imaging can help place the needle and, hence, therapeutic medication more accurately, there is still debate about whether or not image-guided procedures result in improved outcomes. This article discusses the advantages and disadvantages of performing US-guided injections and describes injection principles and techniques. Studies examining the efficacy of US-guided procedures are reviewed.