The invention provides methods and compositions for reducing platelet activation, platelet aggregation and thrombosis. The invention further provides compositions and methods for treating or preventing diseases or disorders in which the pathology of the disease or disorder involves one or more of platelet activation, platelet aggregation and thrombus formation. The invention additionally relates to the use of protein palmitoylation inhibitors for the reduction of platelet activation, platelet aggregation and thrombosis, as well as to the use of protein palmitoylation as a target for the identification of inhibitors of platelet activation, platelet aggregation and thrombosis.