Interactions between human platelets and leukocytes occur in physiological and pathological inflammation, hemostasis, and thrombosis. There is evidence that platelet–leukocyte interactions may be central mechanisms in atherosclerosis and its complications, and also in a variety of other acute and chronic diseases. In addition, models based on interactions of platelets and leukocytes are informative discovery tools that have yielded new insights relevant to human cell functions and cell–cell signaling and information transfer. This short article focuses on interactions between platelets and myeloid leukocytes and profiles some of the key pathways, mechanisms, and outcomes in these cellular dialogues.