In their natural environment, plants interact with many different organisms. The nature of these interactions may range from positive, for example interactions with pollinators, to negative, such as interactions with pathogens and herbivores. In this special issue, the contributors provide several examples of how plants manage both positive and negative biotic interactions. This review aims to relate their findings to what we know about the complex natural environments in which plants have evolved. Molecular analyses of plant genomes and expression profiles have shown how intricately plants may regulate responses to single or multiple biotic interactions. Plant responses are fine-tuned by signalling hormone interactions. When multiple organisms interact with a single plant this may result in antagonistic or synergistic effects. The emerging fields of ecogenomics and metabolomics undoubtedly will refine our understanding of the multilayered regulation that plants use to manage relationships with their biotic environment. However, we can only understand why plants have such an intricate regulatory apparatus if we consider the ecological context of plant biotic interactions.