Despite improvements in guidewire technologies, the traditional antegrade wire escalation approach to chronic total occlusion (CTO) recanalization is successful in only 60-80% of selected cases. In particular, long, calcified, and tortuous occlusions are less successfully approached with a true-to-true lumen approach. Frequently, the guidewire tracks into the subadventitial space, with no guarantee of distal re-entry into the true lumen. The ability to manage the subadventitial space has been a key step in the tremendous improvement in success rates of contemporary CTO percutaneous coronary intervention (PCI), whether operating antegradely or retrogradely. A modern approach to CTO PCI involves understanding the concept of "vessel architecture," which is based on the distinction between coronary structures (occlusive plaque, comprising the disrupted intima and media, and the outer adventitia) and extravascular space. The vessel architecture represents a safe work environment for guidewire and device manipulation. This review provides an anatomy-based description of the concept of vessel architecture, along with a historical perspective of subadventitial techniques for CTO PCI, and outcome data of CTO PCI utilizing the subadventitial space. © 2017 Wiley Periodicals, Inc.