Purpose of Review <p>This review aims to highlight the current trends in discovering cereblon-based PROTAC molecules, including their preclinical or clinical progress, and prospects in combating cancer.</p> Recent Findings <p>Protease-targeted chimeras represent an innovative technology of significant interest to the researchers. These molecules are heterobifunctional, comprising an E3 ligase ligand and a small-molecule inhibitor, designed to recruit a specific protein of interest for degradation via the ubiquitin-proteasome system.</p> <p>Numerous PROTACs, based on small-molecule inhibitors, have been developed and shown their efficiency in targeting various diseases. Among them, cereblon-based PROTACs have collected considerable attention for their encouraging utility. CRBN-based PROTACs, such as well-known <i>ARV-110</i> and <i>ARV-471</i>, are conspicuous for their potential therapeutic mediation. The latest advancements in anti-cancer PROTAC development have been reviewed.</p> Summary <p>Many researchers have investigated PROTAC technology globally in recent years, and the published results are overviewed in this manuscript. The underlined potential drugs, such as AR, ER, BCL6, IRAK4, BTK, CDK, TRK, and BRAF degraders, demonstrate significant clinical potential in cancer treatment.</p>