Nanomaterial-based sonodynamic therapy (SDT) has gained increasing attention in recent years. These ultrasound-sensitive nanomaterials encompass nanoparticles loaded with organic sonosensitizer molecules, inorganic nano-sonosensitizers, and organic-inorganic hybrid nano-sonosensitizers. Upon ultrasound exposure, sonosensitizers are activated by the sonoluminescence emitted during cavitation microbubble collapse, leading to the production of reactive oxygen species (ROS) and free radicals, analogous to the photodynamic effect. The mechanical forces and high temperatures generated by ultrasound-induced cavitation may be also important contributors to SDT. Moreover, ultrasound exhibits superior tissue penetration compared to external excitation light. This chapter introduces the concept and mechanisms of SDT, highlights different categories of nano-sonosensitizers for tumor SDT, and discusses the advantages, limitation, and present challenges associated with SDT.