The PFA-100 (platelet function analyzer) is a relatively new tool for the investigation of primary hemostasis. This article reviews the history of the PFA-100 and details its clinical utility in several settings. The PFA-100 was first introduced to us in 1995 in an issue of Seminars in Thrombosis And Hemostasis, which included data from a field trial headed by Dr. Eberhard Mammen. Since that time, the PFA-100 has featured in nearly 500 publications and some 35 reviews. The PFA-100 has potential utility in monitoring antiplatelet therapy (including aspirin) and as a screening tool for investigating possible von Willebrand disease (VWD) and various platelet disorders. The PFA-100 also has potential value for monitoring DDAVP (desmopressin) therapy in both VWD and functional platelet disorders. Most recent attention has focused on sensitivity to antiplatelet medication, where a new language has also emerged, with researchers talking about "aspirin resistance," "aspirin responsiveness," and "aspirin nonresponsiveness." Ultimately, the greatest strengths of the PFA-100 are its simplicity in use and excellent sensitivity to various hemostatic disturbances. However, because it is a "global" test system for primary hemostasis, this also creates a significant limitation because the PFA-100 is not specific for, nor predictive of, any particular disorder. However, used appropriately, the PFA-100 can be considered a worthwhile addition to hemostasis laboratories involved in the identification or therapeutic monitoring of primary hemostatic disorders. The potential future applications for this simple instrument are also briefly assessed.