The Acceptance and Action Questionnaire—Substance Abuse (AAQ-SA) is an 18-item self-report instrument designed to measure psychological flexibility in substance-abusing populations. Psychological flexibility is defined as the ability to engage with the current moment with conscious awareness and to adapt or persist in behavior based on whether it aligns with one’s core values. Being the core construct targeted in acceptance and commitment therapy (ACT), enhancement of psychological flexibility is thought to indicate treatment effectiveness in the context of ACT. The AAQ-SA is intended to be used as a tool for relevant clinical research and practice. Evidence suggests that psychological flexibility likely plays a key role in managing substance use disorder (SUD) psychopathology, as enhancement of psychological flexibility correlates with improvement in the symptomatology of a variety of psychological difficulties, and there are promising results associated with ACT treatment for substance-abusing populations. This chapter provides an overview of the theoretical framework and therapeutic context of psychological flexibility. Furthermore, the developmental process of the AAQ-SA and its psychometric properties are outlined. The translated versions of the AAQ-SA are discussed, providing an overview of differences in item count, subscales, validation samples, and scoring instructions. This is followed by a discussion on cultural aspects that need to be considered when using the tool, and finally, limitations, recommendations for future research, and concluding remarks on the AAQ-SA.