Adrenocorticotropic hormone (ACTH) is secreted by corticotrophic cells in pulsatile bursts. This paper reviews the extant literature on the phenomenon of pulsatile ACTH after addressing basic issues of hormone pulsatility in neuroendocrine systems. The following themes emerged from reviewing 51 studies measuring plasma ACTH at intervals of 20 min or less: marked inter-individual variability in the pattern of ACTH, the dependence of pulse identification on sampling frequency, the similarity in ACTH pulse amplitude and frequency across species, and the predominance of amplitude over frequency changes in ACTH pulses in altered physiological states. As the hypothalamic-pituitary-adrenocortical (HPA) axis plays a critical role in orchestrating adaptation and survival, the ability to modulate the shape of ACTH signals may prove to be an important means of transmitting complex information to ACTH responsive cells. The clinical and neurobiological significance of temporal alterations in ACTH secretion represents an area for future investigation.