The Hedgehog signaling pathway is highly conserved and plays an essential role in the embryonic development of a wide variety of organs. In adult tissues, such as the central nervous system, it may also be required for homeostasis and repair following injury. The role of Hedgehog signaling in regulating hematopoiesis is not entirely clear. Evidence has shown that Hedgehog signaling is required for both primitive hematopoiesis in the developing embryo, as well as for definitive hematopoiesis in the adult. However, several studies also suggest that Hedgehog pathway activity is completely dispensable in postnatal hematopoiesis. In this review, we discuss the current understanding of Hedgehog signaling in vertebrate hematopoiesis, as well as the contradictory findings that have been reported.