Hematopoietic stem cells (HSCs) are indispensable for the treatment of patients with hematological disorders such as leukemia. However, the amount of available transplantable HSCs is limited. Therefore, new approaches to multiply HSCs in the laboratory are needed. Promising biomimetic technologies for HSC expansion are currently developed. This feature article gives an insight into the significance of this approach and introduces the essential building blocks (cells, matrix, and scaffolds) of biomimetic materials. Some recent strategies are highlighted and the challenges and possible applications of such materials are discussed.