Megakaryocytes are the largest cell in the bone marrow where they are classically responsible for homeostatic platelet production. However, megakaryocytes have been found in many extramedullary organs including prominently in the lung. Historical and more recent studies have consolidated on a working model of a bone marrow–lung partnership in platelet biogenesis whereby medullary megakaryocytes can embolize to the lung for efficient platelet production. Megakaryocytes are also diverse in their phenotypes with extramedullary megakaryocytes adopting local tissue cues to impart immune-like functions. In disease states, the sites of platelet production may change including a more prominent role of extramedullary sites such as the spleen. This chapter will summarize this field and point to the areas of controversy and need for future study.