Several landmark clinical trials of endovascular therapy for acute ischemic stroke have recently jolted the concerted multidisciplinary efforts to develop effective revascularization strategies. Further consideration of these four endovascular stroke trials published in the last year suggests a more fundamental question: are these trials of specific treatments or have the results simply reflected the importance of underlying pathophysiology? Data from IMS III, MR RESCUE, SWIFT and TREVO2 consistently demonstrate the dramatic impact of collateral perfusion in acute ischemic stroke. Such collateral, or parallel, trials of the underlying pathophysiology in stroke reveal that diagnosis or selection of optimal candidates may be paramount to the specific drug or device therapy. Future trials of endovascular therapies may harness the influential role of collaterals as critical selection criteria for intervention, with triage based on imaging rather than time alone. Treating the optimal patient may be more important than chasing an elusive magical therapy.