A growing number of evidence shows that pathological lesions put their own molecular signatures on their tissues and blood vessels. Peptide probes that recognize such molecular signatures can be used in targeted delivery of imaging agents and therapeutics to the diseased tissue. Peptides have smaller size and in turn may exert better tissue penetration than bulky antibodies. Using phage displayed-random peptide libraries, for example, we have identified an IL-4 receptor-binding peptide-1 (IL4rPep-1, CRKRLDRNC). IL-4 receptor (IL4R) is known to be over-expressed on many types of human cancer cells including lung cancer. IL4rPep-1 selectively bound to H226 lung tumor cells that over-express IL4R, while little binding was observed in H460 lung tumor cells that express IL4R at low levels. In vivo fluorescence imaging detected higher levels of homing of IL4R-targeted, fluorescent liposomes to a subcutaneous H226 tumor of mice than that of untargeted liposomes. In addition, IL4R-targeted liposomes containing doxorubicin showed more efficient anti-tumor growth activity than untargeted liposomes. These results suggest that the molecular signature-targeted peptide-mediated imaging and drug delivery is a useful tool for cancer detection and therapy.