Spinal cord injury is widely regarded as one of the leading causes of long-term disability, with approximately 15.4 million people affected worldwide in 2021, due to irreversible neurodegenerative changes. Despite the lack of an effective therapy, research efforts over the years have significantly improved the quality of life for patients living with this damage. To enhance our understanding of this complex and debilitating condition and to develop more effective treatments, scientists have been using animal models of spinal cord lesion since 1911, and, in more recent times, human models have also been explored. While considerable advancements have been made, especially in enhancing the quality of life for affected individuals, an effective cure remains elusive. There is still much research to be conducted, and new strategies are currently being applied, particularly with the growth of bioengineering techniques. This chapter reviews the different models used in spinal cord injury research, highlights the current state of knowledge about spinal cord injury—especially with respect to neurodegenerative lesions, such as hereditary spastic paraplegias and syringomyelia—and provides a forward-looking perspective on the future directions in this field of study.