Anxiety disorders are prevalent and debilitating conditions characterized by excessive concern and fear, affecting thoughts, behaviors, and sensations. A critical component of anxiety is arousal, a complex process involving alertness regulation and stimulus salience modulation. While arousal is adaptive in normal circumstances, dysregulation can lead to hypoarousal or hyperarousal, affecting response selection and threat perception. This chapter reviews challenges in studying arousal in preclinical anxiety models, emphasizing the need for multicomponent measurement and analysis. Novel methodologies integrating physiological measurement with activity tracking of neurons with single-cell resolution in awake animals are discussed, with emphasis in current challenges. Understanding these mechanisms is crucial for developing effective treatments for anxiety disorders.