Novel drugs and treatment modalities are urgently needed to further improve survival of children with cancer. In medical oncology, an increased understanding of the molecular basis of cancer is driving the development of new drugs that target relevant signaling pathways in cancer cells and tumor microenvironment. Small-molecule modulators of signal transduction and monoclonal antibodies against various cellular targets have been approved in adult cancers in recent years. These drugs are now starting to be considered for the use in children. Despite the biological differences between adult and pediatric cancers, common cellular pathways have emerged from experimental research. Thus, insights into clinical experience with molecular targeted drugs in adults may help to accelerate progress in pediatric oncology. Here, the authors review molecules and pathways for which drugs are approved for adult cancer treatment and provide links to existing and potential applications in pediatric oncology.