Multidrug-resistant bacteria have emerged in both community and hospital settings, partly due to the misuse of antibiotics. The inventory of viable antibiotics is rapidly declining, and efforts toward discovering newer antibiotics are not yielding the desired outcomes. Therefore, alternate antibacterial therapies based on physical mechanisms such as light and ultrasound are being explored. Sonodynamic therapy (SDT) is an emerging therapeutic approach that involves exposing target tissues to a nontoxic sensitizing chemical and low-intensity ultrasound. SDT can enable site-specific cytotoxicity by producing reactive oxygen species (ROS) in response to ultrasound, which can be harnessed for treating bacterial infections. This approach can potentially be used for both superficial and deep-seated microbial infections. The majority of the sonosensitizers reported are nonpolar, exhibiting limited bioavailability and a high clearance rate in the body. Therefore, targeted delivery agents such as nanoparticle composites, liposomes, and microbubbles are being investigated. This article reviews recent developments in antibacterial sonodynamic therapy, emphasizing biophysical and chemical mechanisms, novel delivery agents, ultrasound exposure and image guidance strategies, and the challenges in the pathway to clinical translation.