Vasoactive intestinal peptide receptors (VIPRs) are members of the G-protein-coupled receptor superfamily. These receptors are overexpressed in many common malignant tumors and play a major role in the progression and angiogenesis of a number of malignancies. Therefore, VIPRs may be a valuable target for the molecular imaging of tumors and therapeutic interventions. The specific natural ligand or its analogs can be labeled with a radionuclide and used for tumor receptor imaging, which could be used to visualize VIPR-related surface protein expression in vivo and to monitor the in vivo effects of molecular drugs on tumors. Moreover, the involvement of VIPRs in malignant transformation and angiogenesis renders them potential therapeutic targets for cancer treatment. A variety of VIP antagonists and cytotoxic VIP conjugates have been synthesized and evaluated for VIPR-targeted molecular therapy. The importance of VIPRs in tumor biology and the ability to predict responses to targeted therapy and monitor drug interventions suggest that VIP receptor-based imaging and treatment will be critical for the early diagnosis and management of cancer. Here, we review the current literature regarding VIPRs and their natural ligands and the involvement of VIPRs in tumor growth and angiogenesis, with an emphasis on the present use of VIPRs for the molecular imaging of tumors and therapies targeting VIPRs.