The Bv8/Prokineticins (PKs) are a new family of peptides identified in frog, fish, reptiles and mammals that signal through two highly homologous G-protein coupled receptors, PKR1 and PKR2. Bv8/PK proteins possess a unique structural motif comprising five disulfide bonds and a completely conserved N-terminal hexapeptide sequence that is essential for the peptide's biological activities. Over the past few years, several biological functions of Bv8/PK proteins have been elucidated. This review considers all the published data on the action and physiological role of this new biological system implicated in angiogenesis and neurogenesis, in reproduction and cancer and in regulating physiological functions that underly circadian rhythms, such as the sleep/wake cycle, hormone secretion and ingestive behaviors. The high expression level of human Bv8/PK2 in bone marrow, lymphoid organs and leukocytes suggested an involvement of these peptides in hematopoiesis and in inflammatory and immunomodulatory processes. Our review highlights the role of the Bv8/PK and their receptor system in setting the pain threshold under normal and pathological conditions.