The functions of the hypothalamus-pituitary-interrenal (HPI) axis in teleosts have been studied primarily in juvenile and adult fish, whereas little is known about the molecular events leading to the onset of the stressor-induced cortisol response during development. Here we summarize a number of studies that have examined changes in the expression of genes encoding proteins critical for the functioning of the HPI axis, and the associated cortisol response in developing zebrafish embryos and larvae. The mRNA transcripts for some of these genes, including corticotropin releasing factor (CRF), proopiomelanocortin (POMC), melanocortin 2 receptor (MC2R), steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleavage (P450scc) have been detected during embryogenesis prior to hatch. The mRNA levels of MC2R, StAR and P450scc are up-regulated immediately prior to the dramatic rise in basal larval cortisol levels after hatch. Although all the components of the HPI axis are expressed and cortisol is synthesized at hatch, a stressor-induced cortisol response was not evident until 97 hpf. We hypothesize that this disconnect in the timing of the basal cortisol synthesis and stressor-induced cortisol synthesis is due to the delayed development of peripheral and central neural inputs relaying stressor stimuli to the hypothalamus. Overall, zebrafish appear to be an excellent model for elucidating the molecular mechanisms leading to the development of the corticoid stress axis in vertebrates.