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Using the ubiquitin\u2010proteasome system, PROTACs allow the selective degradation of disease\u2010causing proteins, including those traditionally deemed \u201cundruggable\u201d by conventional small\u2010molecule inhibitors. By catalytically eliminating rather than inhibiting proteins, PROTACs provide sustained target suppression with lower doses and reduced toxicity. Their bifunctional design linking a protein of interest to an E3 ligase drives targeted ubiquitination and subsequent proteasomal degradation. Recent progress demonstrates promise in treating solid and hematologic malignancies, with several candidates advancing to clinical trials. This review provides a comprehensive overview of developing PROTACs, from understanding their mechanism to clinical applications, and highlights their emerging role in overcoming drug resistance and advancing the limits of cancer treatment. 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