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By harnessing the inverse piezoelectric effect, ultrasound generates mechanical waves that trigger acoustic cavitation in liquid media, producing localized hotspots of extreme temperature and pressure that can be exploited to activate rationally designed metal complexes through distinct and complementary mechanisms. This review provides a comprehensive analysis of two primary therapeutic modalities enabled by this approach. In sonodynamic therapy, metal centers function as sonosensitizers, generating cytotoxic reactive oxygen species through sonoluminescence\u2010mediated energy transfer. In ultrasound\u2010induced ligand release, the mechanochemical potential of metallocenes and coordination polymers is exploited, whereby cavitation\u2010induced shear forces drive heterolytic metal\u2013ligand bond scission to achieve spatially controlled release of bioactive payloads and catalysts. 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