Here, by Chapter 196 of a volume exploring the endothelium in medicine, it has become clear that this is an astonishingly diverse and far-reaching subject. Identified for the first time only at the end of the nineteenth century, the once seemingly simple and passive cell layer is now understood to represent a dynamic system that reflects and determines much about health and function for humans and other vertebrate species. This collection of chapters shows how far we have come in our understanding, and also how rich the opportunities are for further study and more effective translation of our understanding into clinical practice.

There is great virtue in bringing together all these topics that would normally reside in the archives of separate disciplines. We have gained many different perspectives of what the endothelium is and how endothelial cells (ECs) come together as a functioning system. By reflecting on the way the endothelium develops and by comparing phenotypes across different species, we gain insights into the alternatives available and what any particular developmental pathway means for the organism. This helps us understand the endothelium as a highly evolved, integrated system. The system is by no means perfect. Rather it is an interlocking “bundle of adaptations,” some of which were born of trade-offs that are no longer applicable. Indeed, the extreme path-dependence of evolutionary change has undoubtedly engendered design flaws that render the modern-day human endothelium highly vulnerable to disease.

The use of metaphors to conceptualize the endothelium is a powerful tool for understanding an otherwise hidden and under-appreciated entity. We hope that the reader will agree that the analogies between endothelium and weather, landscape, and urban design are at the same time provocative and illuminating.