Hematopoietic stem cells (HSCs) undergo expansion and differentiation, giving rise to all terminally differentiated blood cells throughout life. HSCs are found in distinct anatomical sites during development, and in adults, hematopoiesis occurs predominantly on the luminal side of the bone cavity in bone marrow. Millions of newly formed blood cells are generated per second to accommodate the short half-life of hematopoietic cells. For this to happen, HSCs must sustain their self-renewal capacity as well as their capability to commit and differentiate toward multiple cell lineages. Development of the hematopoietic system is finely regulated as the animal ages, so that it does not become exhausted or misdirected. This review covers aspects of hematopoietic development from the embryonic period through adult life in relation to development of dendritic cells. It also considers a role for HSCs in extramedullary sites and their possible role in myelopoiesis, with formation of tissue-specific antigen-presenting cells.