The rapid production of reactive oxygen species (ROS) upon pathogen attack is generally considered a defense mechanism for microbial killing and an initiation of host defense responses in plants and animals. In this issue, Siddique et al. show that nicotinamide adenine dinucleotide phosphate oxidase–derived ROS function as a pathogenicity factor to promote the roundworm nematode infection in Arabidopsis thaliana, revealing the complex action of ROS in host-pathogen interactions.