Research over the last decades has provided us with a better understanding of the biology of solid tumors. In some solid tumor malignancies single molecular events leading to malignant transformation have been identified, whilst in others multiple pathways seem to play a role simultaneously. The delineation of such pathways has led to the identification of therapeutic targets. Multiple compounds are available now to treat those molecular aberrations. With the wider use of newer biologic therapies, the understanding of biologic characteristics predicting a clinical response has broadened. This review focuses on the clinical management of gastrointestinal stromal tumors as well as hepatocellular, non small cell lung, renal cell and breast cancer with small molecule tyrosine kinase inhibitors, integrating some of the clinical advances with monoclonal antibody therapies in solid tumor malignancies. It highlights recent advances in relevant biomarkers to predict efficacy of biologic therapies and elaborates on their relevance in the clinical management of patients with solid tumor malignancies. J. Surg. Oncol. 2011;103:574–586. © 2011 Wiley-Liss, Inc.