Induced protein degradation is an emerging drug discovery paradigm that allows the targeted removal of proteins, offering advantages over traditional small-molecule strategies. This approach, which is 'event-driven', involves drug binding that tags the target protein for elimination. Technologies such as proteolysis-targeting chimeras (PROTACs) and hydrophobic tagging (HyT) are being explored for their potential to degrade proteins that are not traditionally druggable, such as transcription factors and scaffolding proteins. PROTACs utilize small-molecule E3 ligase ligands to induce proximity-induced ubiquitination and degradation of target proteins, while HyT employs hydrophobic moieties to mimic a partially unfolded protein state, co-opting the cellular quality control system for degradation. Both approaches offer the potential to target a broader range of proteins than traditional inhibitors, with PROTACs showing particular promise due to their ability to induce sub-stoichiometric degradation. Despite challenges such as poor bioavailability and off-target effects, PROTACs have shown significant potential in preclinical studies, with several compounds in clinical trials. The development of PROTACs and HyT technologies represents a shift from 'occupancy-driven' to 'event-driven' pharmacology, offering new opportunities for targeting previously intractable proteins. The field is rapidly evolving, with ongoing research aimed at improving the specificity, efficacy, and clinical applicability of these technologies.Induced protein degradation is an emerging drug discovery paradigm that allows the targeted removal of proteins, offering advantages over traditional small-molecule strategies. This approach, which is 'event-driven', involves drug binding that tags the target protein for elimination. Technologies such as proteolysis-targeting chimeras (PROTACs) and hydrophobic tagging (HyT) are being explored for their potential to degrade proteins that are not traditionally druggable, such as transcription factors and scaffolding proteins. PROTACs utilize small-molecule E3 ligase ligands to induce proximity-induced ubiquitination and degradation of target proteins, while HyT employs hydrophobic moieties to mimic a partially unfolded protein state, co-opting the cellular quality control system for degradation. Both approaches offer the potential to target a broader range of proteins than traditional inhibitors, with PROTACs showing particular promise due to their ability to induce sub-stoichiometric degradation. Despite challenges such as poor bioavailability and off-target effects, PROTACs have shown significant potential in preclinical studies, with several compounds in clinical trials. The development of PROTACs and HyT technologies represents a shift from 'occupancy-driven' to 'event-driven' pharmacology, offering new opportunities for targeting previously intractable proteins. The field is rapidly evolving, with ongoing research aimed at improving the specificity, efficacy, and clinical applicability of these technologies.