Strange fits of passion I have known… (W Wordsworth, ‘Strange fits of passion’.) bHLH–PAS proteins are regulators of developmental and physiological events that are well conserved between vertebrates and invertebrates. Recent studies using mouse knockouts of bHLH–PAS genes have provided novel insight into the roles of hypoxia inducible factors in controlling oxygen-regulated development and homeostasis, and the role of Single-minded-1 in regulating development and transcription in the hypothalamus. The Drosophilaspineless and vertebrate Aryl hydrocarbon receptor bHLH–PAS orthologs both function in chemosensory processes, but in fundamentally different ways. Spineless controls antennal, limb, and sensory cell development, whereas the Aryl hydrocarbon receptor regulates the response to toxin metabolism. Structural analyses of the PAS domain provide insight into how this interaction domain can act as ligand-binding environmental sensor and signal transducer.