Interpersonal workplace mistreatment (IWM) is a pervasive issue with varied co-worker reactions. Despite significant growth in IWM research, understanding co-workers' responses remains challenging due to scattered research streams and a focus on isolated components. Therefore, this integrative review synthesizes the existing literature to examine when and how co-workers respond to IWM. We identify key factors influencing both the intention and actual behavior of co-workers when initially witnessing IWM. These factors are categorized into eight overarching individual (perceived responsibility, emotion and affect, personal characteristics) and contextual themes (social relationships, risks and costs considerations, workplace characteristics, target characteristics, characteristics of the perpetrator and the act of IWM). By integrating these factors into a comprehensive framework drawing on dual processing accounts, we highlight the complex interplay between cognitive and affective processes in shaping co-worker responses. Understanding these dynamics is crucial for designing effective intervention programs that encourage co-workers to counteract IWM. Our findings offer valuable theoretical insights and practical implications for fostering a more supportive and just workplace environment.