Several studies have revealed that nitric oxide (NO), an endogenous mediator in diverse physiological processes, is produced in plants exposed to the toxic metal cadmium (Cd). It was first shown that exogenously applied NO protects plant tissues against the oxidative damages triggered by Cd, suggesting a putative role for NO in counteracting the deleterious effects of Cd. More recently, our team as well as other laboratories challenged this view and demonstrated that endogenously produced NO promotes the metal-induced reduction of root growth. We investigated more thoroughly the role of NO in mediating Cd effects in roots. We have shown that in Arabidopsis thaliana, the Cd-mediated NO production is sensitive to mammalian NO synthase inhibitors and occurs downstream of IRT1, a major iron transporter also involved in the uptake of Cd. Our data support a model in which this production might be related to the iron deprivation caused by Cd. Accordingly, we found that NO up-regulates the expression of genes encoding proteins related to iron acquisition, including IRT1. This process might explain the ability of NO to amplify Cd uptake and, consequently, the toxic effects of the metal.