The concepts of tailored therapy according to genetic profiling and response based on minimal residual disease evaluation during therapy are attracting increasing interest in modern clinical oncology. Children with acute lymphoblastic leukemia are being stratified to various treatment arms with different intensities according to the genetic characteristics of their leukemia and their response to therapy as measured by real-time polymerase chain reaction. Our ability to quickly identify patients with Ewing sarcoma who have a poor prognosis, and to offer them aggressive therapeutic modalities, such as stem cell transplantation, may result in an improved cure rate. Based on the knowledge gained by gene expression profiling and gene silencing techniques we can expect the emergence of new specific drugs that will target malignant cells without causing damage to normal tissue, resulting in improved cancer therapy.