Clinical problems of the human spine have a high prevalence, affecting more than 25.5 M persons 2012. Older adults, in particular, form a continuously growing age group, with 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 the growing interest for biomechanical research on the spine during the last decades however, many clinical problems remain largely unsolved due to the 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 the ever-growing computer power and imaging devices, the development of FE models has become widespread and have allowed 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). These have thus emerged as powerful and reliable tools with considerable applications in surgery planning, in studying the etiology, progression and effects of spinal deformities and intervertebral disc. These models have enhanced our understanding of the spine and will continue to do so in the future. In our group, numerical work performed using of a FE modeling has highlighted the paramount influence of both geometric patient-specific modeling and in-vivo personalization of tissue mechanical properties. There are many exciting avenues for future research. Amongst these, the question of the validation of computational modeling and simulation with the perspective of supporting the development of medical devices is central.