Increasing evidence suggests that natriuretic peptides (NPs) play diverse roles in mammals, including renal hemodynamics, neuroendocrine, and cardiovascular functions. Collectively, NPs are classified as hypotensive hormones; the main actions of NPs are implicated in eliciting natriuretic, diuretic, steroidogenic, antiproliferative, and vasorelaxant effects, important factors in the control of body fluid volume and blood pressure homeostasis. One of the principal loci involved in the regulatory actions of NPs is their cognate plasma membrane receptor molecules, which are activated by binding with specific NPs. Interaction of NPs with their receptors plays a central role in physiology and pathophysiology of hypertension and cardiovascular disorders. Gaining insight into the intricacies of NPs-specific receptor signaling pathways is of pivotal importance for understanding both hormone-receptor biology and the disease states arising from abnormal hormone receptor interplay. During the last decade there has been a surge in interest in NP receptors; consequently, a wealth of information has emerged concerning molecular structure and function, signaling mechanisms, and use of transgenics and gene-targeted mouse models. The objective of this present review is to summarize and document the previous findings and recent discoveries in the field of the natriuretic peptide hormone family and receptor systems with emphasis on the structure-function relationship, signaling mechanisms, and the physiological and pathophysiological significance in health and disease.