Plants play a key role in the sustainability of life on earth. They fix the solar energy that drives nearly all living processes. As a result, plants are members of complex communities and interact both with antagonists and beneficial organisms. To defend themselves against harmful pathogens and insects, plants have evolved a sophisticated immune system to perceive alien organisms, and to translate this perception into defense. The plant immune system is based on a surprisingly complex defense signaling network that is highly flexible in its capacity to recognize and respond to the invader encountered. Plant hormones and volatile organic compounds emerged as important signaling molecules in local and systemic induced defense responses to pathogen or insect attack. Beneficial relationships between plants and microorganisms are frequent in nature as well, improving plant growth or helping the plant to overcome biotic or abiotic stress. Beneficial associations include root-colonizing microbes, such as plant growthpromoting rhizobacteria and fungi, and mycorrhizal fungi that form a symbiosis with ∼80% of all plant species. These ecologically and agriculturally important beneficial associations are based on the exchange of resources between the plant and the mutualist. Each gram of soil contains billions of microbes. However, the microbial community on plant roots is very different from that in bulk soil. Hence, plants are able to recruit specific microbes from the soil to their roots. The establishment of beneficial associations requires mutual recognition and a high degree of coordination of plant and microbial responses through a continuous molecular dialog between the plant and the beneficial. Because beneficial microbes are recognized as alien organisms, active interference with the plant immune system is fundamental for the establishment of intimate mutualistic relationships. An important question in plant defense signaling research is: how do plants integrate signals induced by pathogens, insect herbivores and beneficial microbes into an adaptive response that maximizes both profitable and protective functions? Molecular and genomic tools are now being used to uncover the complexity of the induced signaling networks that have evolved during the arms races between plants and the organisms with which they intimately interact. To understand the functioning of this complex signaling network in nature, molecular biologists and ecologists have joined forces to place molecular mechanisms of induced plant defenses in an ecological perspective. Exciting new discoveries have greatly advanced our understanding of how the co-evolutionary arms race between plants and its social network has shaped the plant immune system into a sophisticated defensive shield capable of warding off the majority of harmful organisms in its environment. Tremendous progress has also been made in the understanding of how plants respond to and benefit from mutualistic soil-borne microbes to maximize growth and survival. With 31 original contributions, this Research Topic provides a snapshot of the current state of the art of the field of induced plant responses to microbial pathogens, insect herbivores, and beneficial root-associated microbes, with a special focus on the translation of molecular mechanisms to ecology and vice versa. In this Research Topic, a nice mix of Mini Reviews, Reviews,