The study of symbiosis is quintessential systems biology. It integrates not only all levels of biological analysis — from molecular to ecological — but also the study of the interplay between organisms in the three domains of life. The development of this field is still in its early stages, but so far, the findings promise to revolutionize the way we view the biotic world. This Essay outlines some of the challenges facing the field and the implications of its development for all of biology.