It has long been known that storage of information in working memory suffers as a function of proactive interference. Here we review the results of experiments using approaches from cognitive neuroscience to reveal a pattern of brain activity that is a signature of proactive interference. Many of these results derive from a single paradigm that requires one to resolve interference from a previous experimental trial. The importance of activation in left inferior frontal cortex is shown repeatedly using this task and other tasks. We review a number of models that might account for the behavioral and imaging findings about proactive interference, raising questions about the adequacy of these models.