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The aim of this review is to explore the state of the art knowledge on the cell biological and molecular pathways that regulate megakaryopoiesis and lead to platelet production.In the last 2 years there has been considerable progress in the elucidation of molecular mechanisms of megakaryocyte development and platelet biogenesis, driven by the application of modern molecular biology approaches to these specialized and unique cells. Studies have for the first time visualized endomitotic spindle dynamics, characterized the maturation of the demarcation membrane system, and delineated the mechanics of organelle transport and microtubule assembly in living megakaryocytes. The role of specific molecules in platelet production has been elucidated in greater detail by combining molecular studies with genetically engineered mice as well as embryonic cell culture systems.This review integrates the latest studies of megakaryocyte development into the molecular pathways that regulate megakaryopoiesis and thrombopoiesis. Decoding the pathways of megakaryopoiesis and platelet production should help revolutionize the management of thrombocytopenia and other platelet disorders.