Targeted protein degradation is a novel chemical modality centered on using pharmacological agents to immediately and selectively alter protein abundance. While there is a lack of research tools to perturb the majority of proteins in the proteome, hybrid chemical-genetic degradation systems have emerged as orthogonal means to modulate protein homeostasis. These degradation-based strategies are highly complementary to widely used genetic approaches, while offering improved target selectivity profiles and enabling functional studies with superior kinetic resolution. One novel strategy, the degradation tag (dTAG) system, uses heterobifunctional small molecule degraders to co-opt the cellular degradation machinery to rapidly and selectively dispose of tagged proteins. This webinar summarizes the dTAG technology platform and highlights case studies demonstrating utility for target-specific protein degradation. The dTAG system is a versatile tool for pre-clinical target validation and biological investigation in cellular and mouse models.