Spinal cord injury (SCI) is a debilitating condition that affects thousands of new individuals each year, the majority of which are males. Males with SCI tend to be injured at an earlier age, mostly during sports or motor vehicle accidents, whereas females tend be injured later in life, particularly in the age group 65 and older. In both experimental and clinical studies, the question as to whether gender affects outcome has been addressed in a variety of patient groups and animal models. Results from experimental paradigms have suggested that a gender bias in outcome exists that favors females and appears to involve the advantageous or disadvantageous effects of the gonadal sex hormones estrogen and progesterone or testosterone, respectively. However, other studies have shown an absence of gender differences in outcome in specific SCI models and work has also questioned the involvement of female sex hormones in the observed outcome improvements in females. Similar controversy exists clinically, in studies that have examined gender disparities in outcome after SCI. The current review examines the experimental and clinical evidence for a gender bias in outcome following SCI and discusses issues that have made it difficult to conclusively answer this question.