In the setting of hematological neoplasms, changes in the bone marrow (BM) stroma might arise from pressure exerted by the neoplastic clone in shaping a supportive microenvironment, or from chronic perturbation of the BM homeostasis. Under such conditions, alterations in the composition of the BM stroma can be profound, and could emerge as relevant prognostic factors. In this Review, we delineate the multifaceted contribution of the BM stroma to the pathobiology of several hematological neoplasms, and discuss the impact of stromal modifications on the natural course of these diseases. Specifically, we highlight the involvement of BM stromal components in lymphoid and myeloid malignancies, and present the most relevant processes responsible for remodeling the BM stroma. The role of bystander BM stromal elements in the setting of hematological neoplasms is discussed, strengthening the rationale for treatment strategies that target the BM stroma.