Platelet alpha-granules are the storage site for the internal membrane glycoprotein P-selectin and for a variety of megakaryocyte-synthesized and plasma-derived soluble proteins. Quantitative and/or qualitative abnormalities in alpha-granules are found in a number of inherited bleeding disorders, including gray platelet syndrome, alphadelta-storage pool deficiency, the Quebec platelet disorder, and in some patients with dysmegakaryopoietic thrombocytopenia. In addition, single alpha-granular protein deficiencies are seen in other bleeding disorders,including factor V deficiency, afibrinogenemia, Glanzmann's thrombasthenia, von Willebrand disease, and plasminogen-activator inhibitor-1 deficiency. The excessive bleeding that occurs in patients with inherited abnormalities of platelet alpha-granules indicates that the proteins stored within this compartment are important for normal hemostasis. The clinical and laboratory features of these different, inherited platelet storage pool disorders suggest unique molecular and biochemical defects are responsible for these conditions. However, the genetic causes of these disorders are largely unknown. This paper reviews our current knowledge of the inherited disorders of platelet alpha-granules.