Significant advances have been made in the treatment, response monitoring, and supportive care of children with cancer. Although few new cytotoxic drugs have been introduce into the treatment regimen of childhood cancers within the last decade, the 5-year survival among all childhood cancers diagnosed in 1996 to 2002 is 79%. Improvement in survival is the result of risk-directed therapy and an enhanced understanding of the heterogeneity or differences among childhood cancers. The heterogeneity of each childhood cancer is based on the molecular profile of the tumor and the child’s individual response to cytotoxic therapy. This article will review the process used in the genetic-molecular profile classification and molecular monitoring of the most common childhood cancer, acute lymphoblastic leukemia (ALL). The effect of germ line polymorphisms on the individual patient’s response will be discussed, as well as the pharmacogenetic testing that should be initiated prior to therapy. Lastly, the article will discuss the effect of the genetic profile and monitoring on nursing practice.