Antiplatelet therapy is of paramount importance in the treatment and prevention of adverse cardiovascular events and stroke. Drug-drug interactions (DDIs) among antiplatelet therapies have been growing in both prevalence and clinical importance. Most DDIs with antiplatelet therapies are pharmacodynamic in nature. DDIs with thienopyridines and proton pump inhibitors have resulted in advisories from regulatory agencies although the full significance of this interaction is unknown. Other DDIs with thienopyridines may potentially exist with statins, calcium channel blockers, and warfarin but lack demonstratable evidence of harm. Aspirin may interact with a variety of medications, including non-steroidal anti-inflammatory agents and angiotensin inhibitors. DDIs requiring some level of intervention may also be present with dipyridamole and cilostazol. Overall, DDIs with antiplatelet drugs are biologically plausible and potentially clinically relevant. However, the full significance of these DDIs is largely unknown due to reliance on research of voluntary reports, registries, and claims databases to determine significance.