Several advances have been made toward understanding the biology of cancer and most of them are due to robust genetic studies that led to the scientific recognition that although many patients have the same type of cancer their tumors may have harbored different molecular alterations. Personalized therapy and the development of advanced techniques of preclinical imaging and new murine models of disease are emerging concepts that are allowing mapping of disease markers in vivo and in some cases also receptor targeted therapy. Aim of this review is to illustrate some emerging models of disease that allow patient tumor implantation in mice for subsequent drug testing and advanced approaches for therapy mediated by preclinical imaging. In particular we discuss targeted therapy mediated by high frequency ultrasound and magnetic resonance, two emerging techniques in molecular preclinical therapy.