The Whooley questionnaire is a brief screening tool used to assess depression in various healthcare settings. It consists of two simple “yes/no” questions, making it easy to administer and score. This chapter provides an overview of its measures and applications. The questionnaire has been recommended by organizations such as the National Institute for Health and Care Excellence (NICE) for use in specific populations, including perinatal women, patients with chronic physical health issues, and those with a history of depression. While its effectiveness has been demonstrated in the perinatal healthcare setting, further research is needed to explore its use in other populations and cultural contexts. Validation studies are necessary along with the development of clear protocols for future assessment and appropriate care pathways for individuals who screen positive. Overall, the Whooley questionnaire offers a practical and time efficient tool for depression screening, with potential applications in a range of healthcare settings.