Recent advances in the development and application of array-based peptide-substrate kinase activity screens show great promise in overcoming the discrepancy between the evaluation of aberrant cell signaling in specific malignancies or even individual patients and the currently available ensemble of highly specific targeted treatment strategies. These developments have the potential to result in a more effective selection of kinase inhibitors and thus optimize mechanism-based patient-specific therapeutic strategies. Given the results from current research on the tumor kinome, generating network views on aberrant tumor cell signaling is critical to meet this challenge.