Abstract: The development of degradable polymers is of significant interest across a wide range of fields from coatings to nanomedicine and tissue engineering. Much progress has been made with conventional polyesters such as polylactide and polycaprolactone. However, the ability to control the degradation of these polymers in different environments is limited and they may degrade more rapidly or more slowly than desired. Many stimuli-responsive polymers have been developed over the past couple of decades, but these polymers typically require many stimuli-mediated events to achieve complete backbone degradation. This presentation will describe our recent work on polyglyoxylates, a new class of self-immolative polymers, that undergo end-to-end backbone depolymerisation in response to the cleavage of a single end-cap from the polymer terminus, thereby affording amplification of the stimulus-mediated event. Polyglyoxylate properties could be tuned by varying the structures of the glyoxylate monomers to afford different pendant groups on the polymers or by performing post-polymerization functionalization. In addition, block copolymers could be prepared using linker end-caps having additional functional groups and these were assembled into stimuli-responsive nanoscale vesicles and micelles. A diverse library of end-caps were developed that were responsive to stimuli including light, heat, pH changes, reducing agents, and reactive oxygen species Unlike conventional stimuli-responsive polymers, it was possible to change the stimuli to which the system responded simply by changing the end-cap. The function of these polyglyoxylates was demonstrated through the incorporation and triggered release of drug molecules from surfactant-stabilized nanoparticles, micelles, and vesicles. In addition, polyglyoxylates were applied as coatings to release chemicals in response to stimuli. Overall, this work demonstrates the versatility and applicability of self-immolative polyglyoxylates across a range of fields.