The isoprostanes are a unique series of prostaglandin-like compounds formed in vivo from the free radical-catalyzed peroxidation of arachidonic acid independent of the cyclooxygenase enzyme. The purpose of this commentary is to summarize the status of our current knowledge regarding the isoprostanes and discuss what we consider to be avenues for further research. Novel aspects related to the biochemistry of isoprostane formation and methods by which these compounds are analyzed, including potential pitfalls that may occur during analysis, are discussed first. The isoprostanes possess potent biological activity, and their potential role in mediating certain aspects of the detrimental effects of oxidant stress is then examined. In addition, evidence is presented that these biological effects may be mediated through interaction with a unique receptor. A considerable portion of this commentary deals with the utility of measuring isoprostanes as markers of oxidant injury both in vitro and in vivo. A number of studies have shown these compounds to be extremely accurate markers of lipid peroxidation in animal models of oxidative stress and have illuminated the role of oxidant injury in association with several human diseases. Finally, based upon our current knowledge of the isoprostanes, directions for future research are proposed.