This paper aimed to discuss functioning, quality of life, (QoL) and lifespan care issues of adolescents and young adults with childhood-onset physical disability from a clinical, scientific, and personal perspective. We present a résumé of results of recently performed studies in rehabilitation-based samples of (young) adults with childhood-onset conditions such as cerebral palsy (CP) and spina bifida (SB), and different models of transition and lifespan care. The studies showed that many young adults with a childhood-onset disability experience health-related problems such as functional deterioration, pain or fatigue, and an inactive lifestyle. A significant number are restricted in participation in work, housing, and intimate relationships. They perceive a lower health-related and global QoL compared with a reference group. In some centres in the UK and the Netherlands specialized outpatient services are available or being developed. In conclusion, transition to adulthood is a critical phase for reaching autonomous participation in adult life. There is an international challenge to incorporate a lifespan perspective in paediatric, transition, and adult health care services for persons with a childhood-onset disability.