In summary, clinical and animal studies demonstrate that the effects of estrogen in the cardiovascular system protect against the development of histologic and clinical atherosclerosis. However, because estrogen affects so many cellular processes (Figure 4), there are many known adverse effects, including oncogenic and potential negative consequences on the vasculature, including procoagulant and plaque-destabilizing effects. Selective estrogen receptor modulators may allow us to target specific pathways that selectively and favorably effect beneficial responses. However, we must first gain a better understanding of the molecular mechanisms by which estrogen induces cellular signals, both genomic and nongenomic, before we can take full advantage of selective estrogen receptor modulators. As our ability to selectively modulate vascular responses to injury improves, it will be imperative that we have the ability to assess vascular structure, function and pathology with more practical, logistically accessible and biologically targeted approaches than those currently available. Such tools will allow us to test a broad spectrum of agents aimed at pharmacologic therapy for vascular disease.