Testing blood for the early detection of cancer promises a non-invasive method to find early, treatable cancers in asymptomatic patients at risk of developing cancer. Tests are based on next-generation sequencing of cell-free DNA from blood and have shown success in detecting cancer in a stage and organ specific manner. Currently the hottest ticket remains GRAIL’s Galleri test, although the acquisition of GRAIL by Illumina is lately making more headlines than the clinical data. Regardless, the promise is enormous and needs to be thoroughly explored for hard to detect conditions such as pancreatic and ovarian cancer, and for cancer with a strong familial component such as breast and colorectal cancer. A well written statement by the American Cancer Society summarizes the potential of multi-cancer early detection and the challenges yet to be overcome.