This chapter contains a brief discussion of cancer prevention and early detection strategies, and addresses some of the controversies around recent clinical trials. It is meant to provide a guide to more detailed reviews for the interested reader rather than summarizing these topics in a comprehensive fashion. As treatment of advanced malignant diseases still results in less satisfactory results than treatment of early-stage disease, the need for reducing the number of patients diagnosed in advanced or incurable stages is obvious. Also, in terms of aggressiveness of treatment, side effects, quality of life, and other aspects of cancer survivorship, less aggressive or intense treatment will result in many advantages. This will also impact on several economical aspects of treatment, even if the cost of cancer screening and/or prevention must be balanced against the cost reduction, i.e., the net health benefits must come at a reasonable cost. Other important aspects that often fuel the discussion include the potential harm and damage associated with, for example, cancer screening (false-positive results, treatment of biologically insignificant lesions that would never threaten the patient’s life, and so on). This leads to the search for tailored strategies targeting populations that are at higher than average risk and resulting in improved health outcomes.