Platelet activation and aggregation are central to haemostasis and thrombus formation. The dysregulation of these processes contributes to cardiovascular disease. Current antiplatelet therapies can cause excessive bleeding, and there are issues with resistance in a subset of patients. Proteolysis Targeting Chimeric molecules (PROTACs) have gained popularity over the last few years owing to their high potency and specificity, including for previously ‘undruggable’ targets. PROTACs employ the cells ubiquitin proteasome system to degrade proteins of interest. This approach is of particular interest in platelet biology given their limited capacity for de novo protein synthesis. In this chapter, we will explore the development of PROTACs and some of the necessary considerations when designing novel degraders. Furthermore, we will detail how a novel PROTAC may be characterised and some of the challenges and opportunities for application of this powerful technology in human platelets as a research tool and as novel therapeutics.