Minimally invasive treatments (MIT) for thyroid disease encompass both chemical (ethanol) and thermal (laser, radiofrequency, and microwave) ablation modalities. Each MIT modality has a unique mechanism of action that ultimately leads to the ablation of the target lesion. Success of each MIT modality should be considered in the context of goals of treatment and target thyroid structure subtype and characteristics. Selection of MIT modality by thyroid lesions subtype is addressed within this chapter. Examination of the mechanisms of action of the most commonly used MIT for thyroid structural disease aids in the development of theoretic advantages of each modality. However, review of the literature to support modality selection by thyroid lesion subtype suggests the theoretic advantages of MIT modalities may be difficult to decipher in real-world practice given heterogeneity of available studies and the dependence of outcomes on operator expertise. Overall, all MIT modalities are effective for the management of carefully selected structural disease of the thyroid.