The polybrominated diphenylethers (PBDEs) are a class of chemicals widely used as flame retardants. Concentrations of PBDEs in some human and marine mammal populations are increasing. The toxicological endpoints of concern for environmental levels of PBDEs are likely to be thyroid hormone disruption, neurodevelopmental deficits and cancer. Unfortunately, the available toxicological evidence for these endpoints is surprisingly limited, given their widespread use, bioaccumulative potential, and structural similarity to thyroid hormones and polychlorinated biphenyls (PCBs). Available evidence suggests that the PBDE congeners likely to bioaccumulate (i.e., those observed in human tissues and other biota) have the propensity to disrupt thyroid hormones, cause neurobehavioral deficits and possibly cause cancer in laboratory animals. It is unclear whether current concentrations of PBDEs in human tissues would be expected to adversely impact human health. Since nearly all individuals are exposed to low levels of PBDEs, the potential health impacts also should include assessment at the population level. This paper summarizes the available toxicological evidence for PBDE-induced thyroid hormone disruption, neurodevelopmental deficits, and, for some congeners, cancer, and provides a perspective on the potential risks of the PBDEs for human health.