Platelets are essential corpuscular blood components required for hemostasis. They are released from precursor cells in the bone marrow by cellular fragmentation into the blood stream. Although some aspects of platelet biogenesis are well known, studying its occurrence in vivo has been mostly unsatisfactory. This article reviews some recent findings: It first introduces current models of thrombopoiesis including open questions on cell biology. Second, it presents current findings on the release of megakaryocytes over the endothelial barrier into the blood stream where platelet production takes place outside the bone marrow. Finally, it reports on the translation of the more basic science into an improved understanding of novel parameters from automated blood counters surveying platelet volume (MPV), distribution width (PDW), mass (PCT) and the immature platelet fraction (IPF) into clinics where platelet counts are often the only accessible parameter to evaluate the risk of bleeding. Combining the comprehension of these parameters with a more refined image of how and where platelets are born might help find the cause and best therapy when platelet counts are low.