Endothelium-derived relaxing factors (EDRFs), including nitric oxide (NO), prostacyclin ($PGI_2$), and endothelium-derived hyperpolarizing factor (EDHF), play pivotal roles in regulating vascular tone. Reduced EDRFs cause impaired endothelium-dependent vasorelaxation, or endothelial dysfunction. Impaired endothelium-dependent vasorelaxation in response to acetylcholine (ACh) is consistently observed in conduit vessels in human patients and experimental animal models of hypertension. Because small resistance arteries are known to produce more than one type of EDRF, the mechanism(s) mediating endothelium-dependent vasorelaxation in small resistance arteries may be different from that observed in conduit vessels under hypertensive conditions, where vasorelaxation is mainly dependent on NO. EDHF has been described as one of the principal mediators of endothelium-dependent vasorelaxation in small resistance arteries in normotensive animals. Furthermore, EDHF appears to become the predominant endothelium-dependent vasorelaxation pathway when the endothelial NO synthase (NOS3)/NO pathway is absent, as in NOS3-knockout mice, whereas some studies have shown that the EDHF pathway is dysfunctional in experimental models of hypertension. This article reviews our current knowledge regarding EDRFs in small arteries under normotensive and hypertensive conditions.