Heme oxygenases, namely heme oxygenase-1 and heme oxygenase-2, have important biological functions in vascular homeostasis. Heme oxygenase and its catabolic products, including bilirubin and carbon monoxide, have been implicated in blood pressure regulation. Increased expression of heme oxygenase exerts multiple protective actions against hypertension-induced vascular injuries. However, the underlining mechanisms of these effects are not entirely clear. We and others have demonstrated that heme oxygenase-1 can modulate production of reactive oxygen species, both in vivo and in vitro, from NADPH oxidase, a major enzymatic source of reactive oxygen species generation in the vascular wall. NADPH oxidase has been implicated in the development of hypertension and hypertension-related organ injuries. In this mini review, we summarize our current understanding of the interactions between heme oxygenase and NADPH oxidase, and we propose that modulation of NADPH oxidase activity by heme oxygenase could be a potential mechanism of the beneficial effects of heme oxygenase in hypertension.