This chapter provides an overview of traumatic spinal cord injury, including epidemiology, pathophysiology, clinical management, and emerging therapeutic strategies. The epidemiology focuses on the global burden of spinal cord injury worldwide. The pathophysiology section describes the acute, subacute, and chronic phase of spinal cord injury, elucidating the complex interplay of primary and secondary injury mechanisms after the initial trauma. In this frame, a special consideration is given to glial responses and sexual dimorphism shedding light on important factors influencing spinal cord injury progression and recovery. Furthermore, this chapter explores the potential of biomarkers for improving diagnostic precision and managing therapeutic interventions. Clinical management is examined and the challenges and prospects after spinal cord injury are discussed. Recent advancements in surgical and rehabilitative approaches as well as recent findings in preclinical studies are presented, highlighting potential promises of neurotechnologies, biomaterials, cell-based therapies, and gene expression modulation. Additionally, the gut–brain axis modulation offers new insights into the communication between the central nervous system and the gut microbiota and its implications for spinal cord injury management. Through the synthesis of multidisciplinary approaches, this chapter aims to promote a better comprehension of spinal cord injury pathophysiology and to encourage innovative methods to improve outcomes and quality of life for patients with this devastating condition.