Transposable elements (TEs) are pervasive genomic sequences that have significantly shaped genome evolution. Initially discovered by Barbara McClintock in maize, TEs are now understood to influence both coding and noncoding regions of the genome, contributing to physiological processes and, when dysregulated, to disease. In humans, TEs such as LINE-1 (L1), Alu elements, and human endogenous retroviruses (HERVs) are differentially regulated throughout development and cellular differentiation. While TE expression is tightly controlled under normal conditions, aberrant reactivation has been associated with a range of pathologies, including neurodegenerative disorders, autoimmune diseases, and malignancies. Recent advances have highlighted the potential of targeting TE activity for therapeutic purposes. Strategies under investigation include the use of small molecules, gene therapies to modulate TE expression, and immunotherapeutic approaches to eliminate cells expressing aberrant TE products. Antiretroviral drugs originally designed to inhibit HIV replication are also being repurposed to target HERV-mediated diseases. In contrast, some studies are attempting to induce expression of TEs to promote an immune response through viral mimicry and target TE-expressing cells for destruction in cancer. This chapter reviews the biological roles of TEs in disease, evaluates current and emerging therapeutic strategies aimed at modulating TE activity, and explores the potential of leveraging TE biology for the development of targeted and personalized therapies.