Neuroinflammation plays an important role in the secondary pathophysiological mechanisms of spinal cord injury (SCI) and can exacerbate the primary trauma and thus worsen recovery. Although some aspects of the immune response are beneficial, it is thought that leukocyte recruitment and activation in the acute phase of injury results in the production of cytotoxic substances that are harmful to the nervous tissue. Therefore, suppression of excessive inflammation in the spinal cord could serve as a therapeutic strategy to attenuate tissue damage. The immunosuppressant methylprednisolone has been used in the setting of SCI, but there are complications which have attenuated the initial enthusiasm. Hence, there is interest in other immunomodulatory approaches, such as intravenous Immunoglobulin G (IVIg). Importantly, IVIg is used clinically for the treatment of several auto-immune neuropathies, such as Guillain-Barre syndrome, chronic inflammatory demyelinating polyneuropathy (CIPD) and Kawasaki disease, with a good safety profile. Thus, it is a promising treatment candidate for SCI. Indeed, IVIg has been shown by our team to attenuate the immune response and result in improved neurobehavioral recovery following cervical SCI in rats through a mechanism that involves the attenuation of neutrophil recruitment and reduction in the levels of cytokines and cytotoxic enzymes Nguyen et al. (J Neuroinflammation 9:224, 2012). Here we review published data in the context of relevant mechanisms of action that have been proposed for IVIg in other conditions. We hope that this discussion will trigger future research to provide supporting evidence for the efficiency and detailed mechanisms of action of this promising drug in the treatment of SCI, and to facilitate its clinical translation.