Granulocyte-colony stimulating factor (G-CSF) is a growth factor which stimulates proliferation, differentiation, and survival of hematopoietic progenitor cells. G-CSF is being used extensively in clinical practice to accelerate recovery of patients from neutropenia after cytotoxic therapy. However, growing evidences have suggested that G-CSF has important non-hematopoietic functions in central nervous system. Recent studies have shown the presence of G-CSF/G-CSF-receptor (G-CSFR) system in the brain, and their roles in neuroprotection and neural tissue repair as well as improvement in functional recovery. The increased expression of G-CSF/G-CSFR on neurons subjected to hypoxia provides evidence that G-CSF may have an autocrine protective signaling mechanism in response to neural injury. G-CSF exerts neuroprotective actions through the inhibition of apoptosis and inflammation and the stimulation of neurogenesis. Moreover, G-CSF has been shown to mobilize bone marrow stem cells into the injured brain improving neural plasticity. In this review, we summarize some of the recent studies on G-CSF and the corresponding signal transduction pathways regulated by G-CSF in neuroprotection.