The nature of traumatic spinal cord injury (SCI) often involves limited recovery and long-term quality of life complications. The initial injury sets off a variety of secondary cascades, which result in an expanded lesion area. Ultimately, the native tissue fails to regenerate. As treatments are developed in the laboratory, the management of this secondary cascade is an important first step in achieving recovery of normal function. Current literature identifies four broad targets for intervention: inflammation, oxidative stress, disruption of the blood-spinal cord barrier, and formation of an inhibitory glial scar. Because of the complex and interconnected nature of these events, strategies that combine multiple therapies together show much promise. Specifically, approaches that rely on biomaterials to perform a variety of functions are generating intense research interest. In this review, we examine each target and discuss how biomaterials are currently used to address them. Overall, we show that there are an impressive amount of biomaterials and combinatorial treatments which show good promise for slowing secondary events and improving outcomes. If more emphasis is placed on growing our understanding of how materials can manage secondary events, treatments for SCI can be designed in an increasingly rational manner, ultimately improving their potential for translation to the clinic.