For decades, neurology, neuropediatrics and pediatric metabolic medicine were traditionally considered predominantly diagnostic disciplines. For cystic fibrosis and congenital immunodeficiencies, too, the majority of those affected have historically been treated almost exclusively symptomatically or supportively. The greatest challenges were and are the lack of causal therapies and the associated limitations in the treatment of the often rare diseases. In the last few years drugs for new, targeted therapies have arrived in routine pediatric care. The first treatment successes of advanced therapy medicinal products (ATMPs) in pediatrics are promising. Diseases that were considered incurable years ago can now be treated and the patients‘quality of life can be dramatically improved. With the increasing use of ATMPs, we are facing new challenges. On the one hand, early diagnosis has a decisive influence on the success of the therapy and the side effect profile. Newborn screening plays an important role in this context. As in recent years, more and more target diseases will be included in screening as treatment options increase. Due to the still limited data on efficacy and safety of ATMPs and the very individual courses of individual patients, an interdisciplinary and multiprofessional team is necessary for optimal care and follow-up. Last but not least, ATMPs, especially gene therapies, are associated with high costs for the healthcare system. Not only the exploding drug costs, but also the specialized intensive effort of therapies and follow-up care call for a broad political and ethical discussion. Further innovative targeted therapies will shape medical action in the coming years and raise hope for those affected.