The event-related potential (ERP) technique has been used for decades to answer important questions about sensory, cognitive, motor, and emotion-related processes in clinical disorders. However, ERP research with clinical populations often involves unique challenges above and beyond the general issues involved in conducting ERP studies in typical research participants. The goal of this paper is to provide an overview of the common challenges that arise in ERP research with clinical populations, including issues in experimental design, recording, analysis, and interpretation of ERPs. In addition, we provide strategies that have proven effective in each of these areas for maximizing the potential of the ERP technique to provide important insights about clinical disorders. The event-related potential (ERP) technique has been used for decades to assess sensory, cognitive, motor, and emotion-related processes in individuals with clinical disorders, and it has great promise for yielding new insights in the future. However, many complex methodological challenges arise in applying this technique to clinical populations, and these challenges must be overcome for the ERP technique to live up to its potential. The goal of this paper is to describe some of the most salient challenges and provide effective strategies for dealing with them. Our own experience has been mainly in schizophrenia, but much of the information presented here applies to any clinical population. We focus our discussion on traditional approaches to ERPs, for which methods been refined over many decades. Information about newer approaches, such as time-frequency analysis, can be found elsewhere (1; 2). We begin with a brief overview of the ERP technique, followed by a discussion of the challenges in designing experiments, practical considerations in recording and analysis, and issues in interpreting ERP effects. The present article is necessarily brief and focused, but broader reviews are available elsewhere (3-11). In addition, we strongly recommend the ERP publication guidelines of the Society for Psychophysiological Research as a supplement to the recommendations in this paper (12).