In adult mammals, the bone marrow microenvironment is defined by close interactions between cells derived from mesenchymal progenitors and cells derived from hematopoietic progenitors. The influence that one population of cells has over the other has been a matter of intense study since it was established that hematopoietic stem cells (HSCs) require support of stromal elements to engraft, self-renew, and progress towards lineage commitment. Within the stromal components, cells of the osteoblastic lineage have the ability to interact with HSCs, and it has been proposed that they could be one of the main cell types responsible for the generation and maintenance of hematopoietic niches. Possible molecular mechanisms involved in the interaction between osteoblastic and hematopoietic cells have been described. However, understanding the relative importance of each one of them, their production by defined cells, and their kinetics of appearance have been limited by the lack of in vivo models allowing the physical and/or temporal dissection of the components of the osteoblastic lineage. Here, we provide a summary of the evidence that have established the importance of osteoblasts in hematopoiesis, and we propose new experimental strategies that could help to define the nature of these interactions.