Over the past two decades, emotion dysregulation—defined as the inability to dampen strong emotional responses in the service of goal-directed behavior—has emerged as a consistent, transdiagnostic vulnerability to psychopathology. Although specific forms of dysregulated emotion vary across disorders (e.g., exuberance, anger, and related approach emotions in externalizing disorders; anxiety, panic, and related avoidance emotions in internalizing disorders), deficits in dampening emotional responses help define many psychiatric conditions. Peripherally, emotion dysregulation is often marked by low tonic (resting) parasympathetic nervous system (PNS) activity, as indexed by respiratory sinus arrhythmia (RSA). In fact, hundreds of studies conducted to date have found low RSA across diverse forms of psychopathology (e.g., anxiety disorders, autism spectrum disorder, conduct disorder, depression, panic disorder, psychotic disorders). Associations between psychopathology and RSA reactivity to laboratory tasks are less consistent. However, wide variability in tasks and psychophysiological methods may explain some of these inconsistencies. This chapter provides an updated summary of this literature, ending with discussion of methodological issues.