Target validation is essential in the PROTAC approach, and ongoing studies should prioritize confirming ternary complex formation using assays conducted under physiologically relevant cellular conditions. Proteomics analyses are among the most valuable tools for elucidating PROTAC mechanisms, selectivity, and outcomes. The authors are optimistic about the future of PROTACs in drug development and their use as probes to confirm target engagement. PROTAC technology holds vast opportunities for future exploration, offering significant potential to further both chemical and biological research.