Mushi: the most basic forms of life in the world. They exist without any goals or purposes aside from simply "being." They are beyond the shackles of the words "good" and "evil." Mushi can exist in countless forms and are capable of mimicking things from the natural world such as plants, diseases, and even phenomena like rainbows. This is, however, just a vague definition of these entities that inhabit the vibrant world of Mushishi, as to even call them a form of life would be an oversimplification. Detailed information on Mushi is scarce because the majority of humans are unaware of their existence. So what are Mushi and why do they exist? This is the question that a Mushishi, Ginko, ponders constantly. Mushishi are those who research Mushi in hopes of understanding their place in the world's hierarchy of life. Ginko chases rumors of occurrences that could be tied to Mushi, all for the sake of finding an answer. It could, after all, lead to the meaning of life itself.

Perceived as strange and feared by man, over time the misshapen ones came to be known as Mushi. Although they harbor no ill intentions towards humans, many suffer from the side effects of their existence and strange nature; exploiting the Mushi without understanding them, even unintentionally, can lead to disaster and strife for any involved. Mushishi Zoku Shou continues the story of Mushishi Ginko on his journey to help the visible world to coexist with the Mushi. During his travels, Ginko discovers various gifted individuals—those cursed by circumstance and those maintaining a fragile symbiosis with the Mushi—inevitably confronting the question of whether humanity, talented and tortured alike, can manage the responsibility of the unseen. Moreover, as a Mushishi, Ginko must learn more about these strange beings and decide if he has the right to interfere with the complex relationships between Mushi and mankind.