Since Levine and then Barker's seminal work mid to late last century demonstrating the importance of early life environment, intensive research has revealed the plasticity, vulnerability and resilience of the developing brain to environmental challenges. In particular, early exposure to infectious pathogens and inflammatory stimuli has a lasting impact on brain and behavior. These data establish clear effects on vulnerability to later disease and neuroinflammatory injury, cognitive function and emotionality, and even responses to pain and susceptibility to metabolic disorders. They also highlight the issues with defining rodent models of complex diseases like autism spectrum disorders and schizophrenia, as well as the complexity of experimental design, for instance when deciding the appropriate allocation of subjects to experimental groups when dealing with whole-litter manipulations in rodents. The studies presented in this special issue of Brain Behavior and Immunity are a collection of the very latest advances in the science of perinatal inflammation and its implications for perinatal programming of brain and behavior.