Reliable detection of early-stage tumors in cancer patients could vastly improve survival rates. Although probes that accumulate in tumors have been developed, effective imaging is often frustrated by a high background of normal tissues. On p. 375, Weissleder and co-workers describe a way of improving the signal intensity of a tumor-imaging system. They used an infrared fluorescent probe coupled to a polymer that is preferentially taken up by tumors. High levels of proteases in tumor cells activate the probe, allowing detection of submillimeter-sized tumors in live rats.