The standard methods for establishing the diagnosis and prognosis of acute leukemias and lymphomas are cytomorphology and cytochemistry in combination with multiparameter immunophenotyping. However, cytogenetics, fluorescence in situ hybridization (FISH), and polymerase chain reaction (PCR)-based assays add important information with respect to biologically defined and prognostically relevant subgroups. Together, a combination of different methods allows a comprehensive diagnosis with relevant clearly defined subentities. It also leads to a better understanding of the respective clinical course of defined disease subtypes and to a more or less disease-specific therapeutic approach. However, not all patients achieve complete remission during treatment, and many of those who do, later develop relapse and treatment-resistant disease. To overcome these problems, the microarray technology, which quantifies gene expression intensities of thousands of genes in a single analysis, holds the potential to become an essential tool for a strictly molecularly defined classification of leukemias and lymphomas. 2It may therefore be used at first as a novel routine method for diagnostic approaches in the near future (1). But even more importantly, it will also reveal new genetic and therapeutically relevant markers and should guide the search for new targets. Gene expression profiling will also improve patient selection to test therapeutic hypothesis most efficiently and may help define dose and schedule determination. This chapter outlines the major steps for gene expression profiling analyses to approach these different goals by starting at a better diagnostic characterization of leukemias and lymphomas hopefully ending up with new targets for individual treatment of the respective patients.