Co-ordinated changes in cardiovascular and respiratory (cardiorespiratory) function are an essential part of many behavioural responses, such as those associated with exercise or defensive behaviour. Various homeostatic reflexes, such as that evoked by a hypoxic challenge, also include co-ordinated cardiorespiratory responses. Understanding the mechanisms within the brainstem (and forebrain) that produce appropriate co-ordinated cardiorespiratory responses, either reflexly evoked or as part of more generalized behavioural responses, has long been a major challenge to physiologists. There are two general hypotheses concerning the organization of the central pathways that can explain how such co-ordinated responses are produced. According to the first hypothesis, brainstem respiratory neurons that control the motor outputs to the respiratory muscles also have outputs to brainstem neurons controlling the sympathetic outflow to the heart and blood vessels. Thus, according to this hypothesis, the increased activity of sympathetic premotor neurons innervating the heart and blood vessels that occurs during certain behaviours or reflex responses is a consequence of the excitation of such neurons by inputs from brainstem respiratory neurons. An alternative hypothesis, however, is that both central respiratory and sympathetic premotor neurons receive inputs from a common set of neurons (i.e. ‘command neurons’), so that increased drive from these command neurons will lead to increased respiratory and sympathetic activity in parallel. This presentation will first briefly review the results of studies from our laboratory as well as other laboratories, on the functional organization of the central pathways subserving the chemoreceptor reflex, as an example of a reflexly-evoked integrated cardiorespiratory response. The presentation will then focus on the alerting or defence response, as an example of an integrated cardiorespiratory response associated with a more generalized behavioural response. With regard to the latter, it is generally accepted that the dorsomedial hypothalamus (DMH) contains neurons that are an essential part of the pathways producing stress-evoked cardiorespiratory responses (diMicco et al. 2002; Dampney et al. 2005). Activation of these neurons results in increased sympathetic vasomotor activity, heart rate and respiratory activity as well as other effects including increased ACTH release (diMicco et al. 2002). It has been shown that sympathetic premotor neurons in the rostral ventrolateral medulla (RVLM) mediate the increased sympathetic vasomotor activity evoked from the DMH, whereas the increase in heart rate is mediated by neurons in the raphe pallidus in the midline medulla (diMicco et al. 2002; Cao et al. 2004; Horiuchi et al. 2004). In addition, activation of DMH neurons also resets the baroreceptor reflex, such that it remains effective, without any decrease in sensitivity, over a higher range of operating pressure (McDowall et al. 2006). It is proposed that this baroreflex re-setting is mediated by a pathway from the DMH to the nucleus tracti solitarii (NTS) in the medulla. The role of the DMH in respiratory regulation has not been studied extensively. We have recently found, however, that DMH activation also increases the rate and amplitude of phrenic nerve activity, in parallel with increases in heart rate and sympathetic vasomotor activity. In reviewing studies on the central mechanisms subserving cardiorespiratory responses reflexly evoked by stimulation of peripheral chemoreceptors, or those evoked from the forebrain, the question will be considered as to what extent the observations of these studies support the hypothesis of ‘command neurons’ with collateral outputs that simultaneously regulate central cardiac, vasomotor and respiratory neurons.