The article provides an ecological and evolutionary perspective on human-microbe mutualism and disease. It highlights the complex and dynamic nature of the human microbiota, which consists of a unique mix of microorganisms that have co-evolved with their human hosts. The authors discuss how mutualistic interactions between humans and their symbiotic bacteria are essential for human health, and how disruptions in these interactions can lead to disease. They emphasize the importance of applying ecological and evolutionary principles to understand and improve human health. The article also explores the evolution of mutualism, the role of the immune system in maintaining mutualistic relationships, and the impact of human activities on the human microbiota. Finally, it outlines future research directions and the need for integrated approaches to understand the complex ecology of human health and disease.The article provides an ecological and evolutionary perspective on human-microbe mutualism and disease. It highlights the complex and dynamic nature of the human microbiota, which consists of a unique mix of microorganisms that have co-evolved with their human hosts. The authors discuss how mutualistic interactions between humans and their symbiotic bacteria are essential for human health, and how disruptions in these interactions can lead to disease. They emphasize the importance of applying ecological and evolutionary principles to understand and improve human health. The article also explores the evolution of mutualism, the role of the immune system in maintaining mutualistic relationships, and the impact of human activities on the human microbiota. Finally, it outlines future research directions and the need for integrated approaches to understand the complex ecology of human health and disease.