In recent years a substantial body of evidence derived from not only preclinical but also clinical studies has accumulated in support of Notch signaling playing important oncogenic roles in several types of cancer. The finding that activating Notch mutations are frequently found in patients suffering from acute lymphoblastic leukemia is one of the best examples for a critical role of Notch signaling in cancer, a fact that motivated many researchers and clinicians to study the role of Notch also in solid tumors. Hence Notch signaling has gained increasing attention as a potential therapeutic target. In this book chapter we would like to discuss our current knowledge of Notch signaling within different types of solid cancers as well as advantages and disadvantages of potential new therapies that try to target the oncogenic properties of Notch signaling.