Survival rates after childhood cancer now reach nearly 80% in developed European countries as a result of more effective therapies and better supportive care, leading to a steady increase in the number of survivors in the population. However, the treatments that have improved survival are harsh and cause serious side-effects that can greatly impact survivors’ quality of life in the long term. The goal of PanCareLIFE is that survivors of cancer diagnosed before age 25 should enjoy the same quality of life and opportunities as their peers who have not had cancer. Using observational studies and molecular genetic investigations PanCareLIFE will investigate late effects that impact fertility and hearing impairment (ototoxicity), and will assess health-related quality of life. Information from PanCareLIFE’s studies will be incorporated into new guidelines for fertility preservation. As the number of survivors with late effects in any one country is small, large cohorts are required for accurate estimation of risk. PanCareLIFE has assembled a team of prominent investigators from 8 European countries who will contribute in total over 12,000 well-characterised research subjects to identify risk factors, both genetic and non-genetic, linked to decrements in fertility and ototoxicity. Quality-of-life studies will evaluate the impact of fertility and ototoxicity. PanCareLIFE will advance the state-of-the-art in survivorship studies by evaluation of large cohorts with observational and genetic tools that will provide better knowledge of individual risk factors. Survivors can then be stratified into groups benefitting from personalized, evidence-based, care; future patients may expect effective therapies to have less severe side effects, and plans for a seamless transition to long-term follow-up care can be made. These approaches will result in better quality of life for survivors of cancer diagnosed at a young age.