Olfactory ensheathing glial cells (OECs) are a specialized type of glia that form a continuously aligned cellular pathway that actively supports unprecedented regeneration of primary olfactory axons from the periphery into the central nervous system. Implantation of OECs stimulates neural repair in experimental models of spinal cord, brain and peripheral nerve injury and delays disease progression in animal models for neurodegenerative diseases like amyotrophic lateral sclerosis. OECs implanted in the injured spinal cord display a plethora of pro-regenerative effects; they promote axonal regeneration, reorganize the glial scar, remyelinate axons, stimulate blood vessel formation, have phagocytic properties and modulate the immune response. Recently genome wide transcriptional profiling and proteomics analysis combined with classical or larger scale "medium-throughput" bioassays have provided novel insights into the molecular mechanism that endow OECs with their pro-regenerative properties. Here we review these studies and show that the gaps that existed in our understanding of the molecular basis of the reparative properties of OECs are narrowing. OECs express functionally connected sets of genes that can be linked to at least 10 distinct processes directly relevant to neural repair. The data indicate that OECs exhibit a range of synergistic cellular activities, including active and passive stimulation of axon regeneration (by secretion of growth factors, axon guidance molecules and basement membrane components) and critical aspects of tissue repair (by structural remodeling and support, modulation of the immune system, enhancement of neurotrophic and antigenic stimuli and by metabolizing toxic macromolecules). Future experimentation will have to further explore the newly acquired knowledge to enhance the therapeutic potential of OECs. © 2014 Elsevier Inc.