This article reviews the conceptualization and empirical evidence of the midlevel process called cognitive defusion. First, it presents examples of cognitive fusion and cognitive defusion definitions that are offered in acceptance and commitment therapy (ACT) manuals; discusses their relationships with other ACT midlevel processes; and offers a relational frame theory (RFT) conceptualization of these processes. Second, it describes the type of cognitive defusion exercises and discusses the basic processes involved in them. Third, it reviews the measurement of cognitive (de)fusion in the form of self-report instruments, behavioral measures, and assessment in the clinical session. Fourth, it reviews the research on cognitive (de)fusion separated in laboratory research, survey research, and the analysis of processes of change in clinical trials. Lastly, it discusses some challenges and future directions in conceptualizing and researching cognitive (de)fusion.