About sixty percent of the US population of those age fifty and older are currently up to date with colorectal cancer screening recommendations. Has this level of screening made a difference for reducing colorectal cancer (CRC) incidence and/or mortality? Randomized controlled trials of guaiac-based fecal occult blood tests, which have relatively low sensitivity but high specificity for CRC, have shown a modest effect but with a long-term reduction in CRC mortality. Newer fecal immunochemical tests are expected to have a greater effect. Randomized controlled trials of flexible sigmoidoscopy have also demonstrated a reduction in CRC mortality. Observational studies of screening colonoscopy suggest an effect of greater than fifty percent reduction in CRC mortality. We have assessed past trends of colorectal cancer screening in the US population which suggest that more than fifty percent of the decline in colorectal cancer mortality can be attributed to the increased acceptance and uptake in colorectal cancer screening. Current and future levels of increased screening could provide for even larger reductions for the USA. Colorectal cancer screening has and will continue to make a significant impact on reducing colorectal cancer mortality.