The colonization of maize (Zea mays L.) and peanut (Arachis hypogaea L.) by the fungal pathogen Aspergillus flavus results in the contamination of kernels with carcinogenic mycotoxins known as aflatoxins leading to economic losses and potential health threats to humans. The regulation of aflatoxin biosynthesis in various Aspergillus spp. has been extensively studied, and has been shown to be related to oxidative stress responses. Given that environmental stresses such as drought and heat stress result in the accumulation of reactive oxygen species (ROS) within host plant tissues, host-derived ROS may play an important role in cross-kingdom communication between host plants and A. flavus. Recent technological advances in plant breeding have provided the tools necessary to study and apply knowledge derived from metabolomic, proteomic, and transcriptomic studies in the context of productive breeding populations. Here, we review the current understanding of the potential roles of environmental stress, ROS, and aflatoxin in the interaction between A. flavus and its host plants, and the current status in molecular breeding and marker discovery for resistance to A. flavus colonization and aflatoxin contamination in maize and peanut. We will also propose future directions and a working model for continuing research efforts linking environmental stress tolerance and aflatoxin contamination resistance in maize and peanut.