This chapter introduces maladaptation, defined as the inadequate adjustment to environmental changes resulting in detrimental behavioral patterns that interfere with optimal functioning. Maladaptation is a defining feature of many psychiatric conditions and a core psychological phenomenon. This chapter then details the general methods researchers and clinicians use to quantify maladaptive behaviors, emphasizing the critical concepts of reliability and validity. Measurement techniques discussed include clinical assessments, personality inventories, self-report questionnaires, and objective cognitive-behavioral paradigms. Finally, this chapter explores the essential role of animal models in investigating the neurobiological underpinnings of maladaptive processes in controlled settings. This section concludes with an overview of the ethical “R’s” of research, replacement, reduction, and refinement, which guide the humane use of animal subjects in scientific study.