Platelet function can be abnormally increased, as in association with vascular events, or defective, as in a variety of clinical settings, or display converse phenotypes with increased and decreased platelet responsiveness, as in myeloproliferative neoplasms. Drugs represent the most frequent cause of platelet dysfunction. While aspirin, ADP receptor antagonists, and integrin αIIbβ3 inhibitors are well-known prototypes of antiplatelet agents, other widely used agents (e.g., nonsteroidal anti-inflammatory drugs, antibiotics, serotonin reuptake inhibitors, and volume expanders) and supplements can also impair platelet function and cause or aggravate hemorrhage. Certain clinical conditions are often associated with qualitative platelet disorders and a bleeding diathesis. Consequently, acquired platelet function defects are far more common in clinical practice than inherited platelet disorders. The pathogenesis of abnormal platelet function is heterogeneous. Platelet dysfunction, sometimes in association with quantitative abnormalities, is present in uremia, liver disease, autoimmune and hematologic disorders, cardiac valvular disease, and extracorporeal settings. Due to their heterogeneity, acquired platelet function disorders will be discussed in relation to their underlying clinical conditions.