Isoprostanes are products of peroxidative attack of membrane lipids. As such, they accumulate to substantial levels in conditions of oxidative stress, including many pulmonary vascular diseases such as acute lung injury and pulmonary hypertension, and are increasingly being used as indicators of disease state and severity. However, our group and others have hypothesized that they are more than inert markers, but may also act as signal transduction molecules. As isomers of prostaglandins, they can exert powerful biological effects on many lung cell types through actions on prostanoid receptors. In this review, we collect many lines of evidence which point to causal roles for the isoprostanes in those disease states.