Clinical problems of the human spine have a high prevalence, affecting more than 25.5 million people in 2012. Older adults, in particular, are susceptible to degenerative spine disorders such as deformities or osteoporosis. A basic requirement for proper management of various spinal disorders, effective injury prevention, and rehabilitation is a detailed knowledge of the fundamental biomechanics of the spine. Despite growing interest in biomechanical research on the spine during the last decades, however, many clinical problems remain largely unsolved, because of poor understanding of the underlying degeneration phenomena and the complexity of the spinal construct. In particular, diagnosis is challenging, because of the lack of tools to quantitatively assess soft tissue alteration, and because the most relevant clinical indices for diagnosis are not clearly established. Driven by ever-growing computer power and imaging devices, the development of FE models has become widespread, allowing scientists to overcome some of the existing shortcomings (invasiveness, complexity of the organization of the biological tissues, and complexity of establishing the loads present in the human spine, for example). These have emerged as powerful and reliable tools with considerable applications in surgery planning, in studying the etiology, progression, and effects of spinal deformities and intervertebral discs. These models have enhanced our understanding of the spine and will continue to do so. In our group, numerical work performed using FE modeling has highlighted the paramount influence of both geometric patient-specific modeling and in vivo personalization of tissue mechanical properties. Among the many exciting avenues for future research is the question of the validation of computational modeling and simulation with the perspective of supporting the development of medical devices.