To date the system of orexin-containing neurons and neurotransmitters orexin A and B were shown to be involved in brain response to stress. Here we review new experimental data about the involvement of orexin neurons in brain reactions to stressors (hunger, hypoglycemia, immobilization, pain, etc.). Recent evidence shows that the release of orexin A and B may affect the secretion of the hypothalamic-pituitary-adrenal axis hormones in response to stressors. Hypothalamic orexin-containing neuron groups depend for activation on applied stimulation. The patterns of morphological and functional changes of orexin-containing neurons, which are localized in various hypothalamic structures, were analyzed after various stressors were applied (eg. restraint stress, cold stress, antigen application). The analysis of the literature and our own data suggest functional identity of populations of orexin-containing neurons in the perifornical part of hypothalamus. The reactions of orexin-sensitive cells of the hypothalamus, midbrain, medulla, spinal cord and immune organs to antigen injections in different doses reflect changes in the functional of orexinergic cells. These data indicate the participation of orexin system in brain reaction to various kinds of stressors.