Mammalian bombesin-like peptides are a small number of regulatory peptides that exert their broad range of biologic functions through specific, high-affinity binding to their respective G protein–coupled receptors, the bombesin receptors. Bombesin-like peptides are widely expressed in the central nervous system and gastrointestinal tract, where important physiologic functions include regulation of satiety, thermoregulation, smooth muscle contraction, and the release of other peptide hormones. Both bombesin-like peptides and their respective bombesin receptors are found aberrantly expressed in some human malignancies, where they may initiate intracellular signals of cell proliferation, differentiation, and migration through autocrine and paracrine mechanisms. This article reviews the molecular biology of bombesin-like peptides and their specific bombesin receptors, and relevant intracellular signaling events in human cancers. Furthermore, clinical applications are summarized, because specific gastrin-releasing peptide receptor antagonists and novel radiolabeled compounds are now introduced as potential tools for the diagnosis and treatment of human cancers bearing functional gastrin-releasing peptide receptors.