Divided into two parts, Part I describes in detail what we know about the genetics, molecular biology, biochemistry and structural biology of Notch, as well as the role of Notch in such processes as angiogenesis and immune surveillance. Without insights gained from these basic studies, rational targeting of Notch in human disease would be impossible. Part II describes the role of Notch and ongoing experimental therapeutic efforts in the most important subtypes of human cancers, organized in a clinically oriented fashion by organs and systems affected