The spinal ligaments are essential connective tissue structures that maintain spinal stability and biomechanical function. Their extracellular matrix (ECM) is composed of collagens, elastin, proteoglycans, and glycosaminoglycans, which together regulate elasticity, tensile strength, and cellular signaling. Degenerative changes in these ligaments—particularly the ligamentum flavum—are associated with aging, repetitive mechanical stress, inflammation, and oxidative damage. These factors disrupt ECM homeostasis, leading to fibrosis, elastin degradation, and in some cases, pathological ossification. This chapter provides a comprehensive analysis of the biochemical architecture of spinal ligaments, emphasizing key molecular pathways involved in degeneration. Special focus is given to the roles of matrix metalloproteinases, transforming growth factor-beta, oxidative stress, and proinflammatory cytokines (e.g., IL-6, TNF-α, IL-17) in driving fibrotic remodeling and structural transformation. Genetic syndromes such as Ehlers-Danlos and Marfan syndrome are also discussed for their impact on ligament integrity. Additionally, the pathomechanisms of ligament ossification and the influence of inflammatory diseases such as ankylosing spondylitis and rheumatoid arthritis are outlined. By integrating histopathological, molecular, and biomechanical perspectives, this chapter highlights the importance of early biochemical markers and emerging therapeutic targets in preventing or reversing spinal ligament degeneration.