Purpose of Review: Acute psychoemotional stress is one of the causes of a sharp increase in blood pressure. However, the question if the stress may promote the hypertensive disease development is still open. This review aims, firstly, to show that the genetically determined enhanced responsiveness to stress is linked to sustained hypertension development and, secondly, to characterize the main physiological mechanisms and genetic factors implicated in the pathogenesis of stress-sensitive hypertension. Recent Findings: Recent findings helped to characterize the main neuroendocrine mechanisms and the specificity of the genetic background contributing to the stress-sensitive hypertension development in the ISIAH rats. Summary: The ISIAH rat strain, which is an original model of the stress-sensitive arterial hypertension, can be considered as “living” proof that the genetic predisposition to increased stress-reactivity can lead to the development of persistent stress-dependent arterial hypertension. The ISIAH rat strain is characterized by the genetically determined enhanced response of the neuroendocrine and renal regulatory systems to stress and is a suitable model that allows one to explore the genetic and physiological mechanisms involved in stress-sensitive hypertension development. There are common genetic loci (QTLs) associated with both basal and stress-induced blood pressure (BP) levels as well as QTLs associated with BP and other traits, which may be related to hypertension development in ISIAH rats. Multiple genes differentially expressed in the target organs/tissues of hypertensive ISIAH and normotensive control rats are associated with many biological processes and metabolic pathways involved in stress response and arterial hypertension. The genotype of ISIAH rats is characterized by numerous specific and common SNPs as compared with other models of hypertensive rats. The results of the studies are valuable for the search for genetic markers specific for stress-induced arterial hypertension, as well as for the selection of new molecular targets that may be potentially useful for prevention and/or therapy of hypertensive disease.