Induced protein degradation by small molecules has emerged as a promising therapeutic strategy, particularly for targeting proteins previously considered "undruggable." Thalidomide analogs, such as lenalidomide and pomalidomide, act as molecular glue degraders, redirecting the CRBN E3 ubiquitin ligase to degrade myeloma-dependency factors, IKZF1 and IKZF3. These compounds have shown clinical success in treating multiple myeloma and del(5q) myelodysplastic syndrome. Beyond molecular glue degraders, other modalities such as heterobifunctional degraders (PROTACs), polymerization-induced degradation, ligand-dependent degradation of nuclear hormone receptors, and disruption of protein interactions are being developed and evaluated. Induced protein degradation involves redirecting ubiquitin ligases to induce selective degradation of target proteins. This approach expands the druggable proteome and enables the elimination of all functions of the degraded protein, both enzymatic and scaffolding. Molecular glues, such as thalidomide analogs, induce proximity between the E3 ligase and target proteins, leading to their ubiquitination and degradation. Other molecular glues, like indisulam, induce degradation of specific proteins through interactions with E3 ligases. Heterobifunctional degraders, such as ARV-471 and NX-2127, target multiple proteins and have shown efficacy in treating various cancers. These degraders can target both enzymatic and scaffolding functions of proteins, offering broader therapeutic potential. Polymerization-induced degradation, exemplified by BCL6 and PML-RARA, involves small molecules inducing polymerization and subsequent ubiquitination and degradation of target proteins. Ligand-induced degradation of nuclear hormone receptors, such as ER and GR, has shown promise in treating cancers and other diseases. Disruption of protein interactions, such as with HSP90 and EZH2, can also lead to protein degradation. Therapeutic targeting of endogenous induced protein degradation mechanisms, such as HIF1α and NRF2, offers opportunities for pharmacological intervention. The field of induced protein degradation has made significant progress, with new strategies emerging for targeting a wide range of disease-modifying proteins. Advances in proteomics, genetic screening, and structural biology are driving the identification of small-molecule degraders. This approach holds great potential for treating a wide range of diseases by expanding the druggable proteome and enabling the degradation of previously undruggable proteins.Induced protein degradation by small molecules has emerged as a promising therapeutic strategy, particularly for targeting proteins previously considered "undruggable." Thalidomide analogs, such as lenalidomide and pomalidomide, act as molecular glue degraders, redirecting the CRBN E3 ubiquitin ligase to degrade myeloma-dependency factors, IKZF1 and IKZF3. These compounds have shown clinical success in treating multiple myeloma and del(5q) myelodysplastic syndrome. Beyond molecular glue degraders, other modalities such as heterobifunctional degraders (PROTACs), polymerization-induced degradation, ligand-dependent degradation of nuclear hormone receptors, and disruption of protein interactions are being developed and evaluated. Induced protein degradation involves redirecting ubiquitin ligases to induce selective degradation of target proteins. This approach expands the druggable proteome and enables the elimination of all functions of the degraded protein, both enzymatic and scaffolding. Molecular glues, such as thalidomide analogs, induce proximity between the E3 ligase and target proteins, leading to their ubiquitination and degradation. Other molecular glues, like indisulam, induce degradation of specific proteins through interactions with E3 ligases. Heterobifunctional degraders, such as ARV-471 and NX-2127, target multiple proteins and have shown efficacy in treating various cancers. These degraders can target both enzymatic and scaffolding functions of proteins, offering broader therapeutic potential. Polymerization-induced degradation, exemplified by BCL6 and PML-RARA, involves small molecules inducing polymerization and subsequent ubiquitination and degradation of target proteins. Ligand-induced degradation of nuclear hormone receptors, such as ER and GR, has shown promise in treating cancers and other diseases. Disruption of protein interactions, such as with HSP90 and EZH2, can also lead to protein degradation. Therapeutic targeting of endogenous induced protein degradation mechanisms, such as HIF1α and NRF2, offers opportunities for pharmacological intervention. The field of induced protein degradation has made significant progress, with new strategies emerging for targeting a wide range of disease-modifying proteins. Advances in proteomics, genetic screening, and structural biology are driving the identification of small-molecule degraders. This approach holds great potential for treating a wide range of diseases by expanding the druggable proteome and enabling the degradation of previously undruggable proteins.