The collateral circulation plays a crucial role in maintaining perfusion to brain tissue in ischemic stroke, which prolongs the time window for effective therapies to be provided and ultimately avoids irreversible damage that may lead to worse clinical outcomes. The understanding of this complex vascular bypass system has advanced greatly in the past few years, yet effective treatments for its potentiation as a therapeutic target remain a challenge. The assessment of the collateral circulation is now part of the routine neuroimaging protocols for acute ischemic stroke, which provides a more complete pathophysiological picture in each patient that allows for a better selection for acute reperfusion therapies and a more accurate prognostication of outcomes, among other potential uses. In this review, we aim to provide a structured and updated approach to the collateral circulation while highlighting ongoing research areas with promising future clinical applications.