Screening for breast cancer using mammography is one of the most common medical tests for women aged 50 and older. In the United States, many protocols initiate mammography at ages 40 or 45. Although cancer screening tests are widely advocated, some systematic reviews find little evidence supporting the most common screening tests. Cancer screening clearly identifies lesions at an earlier stage. Yet, when evaluated against cancer-specific or all-cause mortality, screening is less likely to be associated with longer life of higher quality of life. This chapter reviews a series of biases, including lead time bias and length bias, that may explain the discrepancy between enthusiasm for cancer screening and clinical trials that have consistently failed to show benefit. We also review potential harms of screening, such as false positive results, unnecessary biopsies, and anxiety. We conclude that more studies are needed, particularly investigations that include a heterogeneous mix of studies participants.