Cooperative integration of laboratory and clinical trial data has provided striking improvement in the treatment of pediatric malignant conditions over the last 2 decades. If attempts are made to individualize therapy to the specific disease and prognostic treatment subgroups for each pediatric malignant condition, the combination of surgery, radiation therapy, and chemotherapy can put the vast majority of patients into a complete clinical remission, with apparent cure for more than half of these patient. Depending on the disease type, treatment failure, when it occurs, is usually the result of recurrent, distant, metastatic disease that is refractory to prior treatment and simultaneously refractory to treatment approaches not yet used for the patient who has had a relapse. The clinical research challenge with these pediatric malignant neoplasms is to identify those children who are harboring microscopic amounts of residual tumor before their relapse and develop effective combined well-tolerated treatment approaches that can be initiated in those patients. These additional treatment approaches should complement rather than duplicate the biologic mechanisms that had been used to initiate remission to eradicate residual tumor without cross resistance. Ongoing laboratory and clinical research approaches are developing and testing the potential of biologic/immunologic therapeutics. The broad application of these principles to clinical oncology will be facilitated by the integrated laboratory-clinical testing that is being accomplished through cooperative pediatric clinical research trials.