Mobilized peripheral blood (PB) is the most common source of hematopoietic stem cells (HSC) for autologous transplantation. Granulocyte colony stimulating factor (G-CSF) is the most commonly used mobilization agent, yet despite its widespread use, a considerable number of patients still fail to mobilize. Recently, a greater understanding of the interactions that regulate HSC homeostasis in the bone marrow (BM) microenvironment has enabled the development of new molecules that mobilize HSC through specific inhibition, modulation or perturbation of these interactions. AMD3100 (plerixafor), a small molecule that selectively inhibits the chemokine receptor CXCR4 is approved for mobilization in combination with G-CSF in patients with Non-Hodgkin’s lymphoma and multiple myeloma. Nevertheless, identifying mobilization strategies that not only enhance HSC number, but are rapid and generate an optimal “mobilized product” for improved transplant outcomes remains an area of clinical importance. In recent times, new agents based on recombinant proteins, peptides and small molecules have been identified as potential candidates for therapeutic HSC mobilization. In this review, we describe the most recent developments in HSC mobilization agents and their potential impact in HSC transplantation.