Personality disorders (PDs) represent enduring patterns of inner experience and behavior that deviate markedly from cultural expectations, significantly impairing social, occupational, and interpersonal functioning. While traditional perspectives have emphasized psychosocial and developmental influences in the etiology of PDs, an expanding body of evidence supports the pivotal role of neurobiological mechanisms, particularly the dysregulation of neurotransmitter systems, in shaping maladaptive personality traits and behaviors. This entry explores the neurochemical underpinnings of PDs, with a specific focus on key neurotransmitters including serotonin, dopamine, norepinephrine, gamma-aminobutyric acid (GABA), and glutamate. Each neurotransmitter system is examined in relation to specific symptom domains and personality traits, such as impulsivity, aggression, emotional dysregulation, and social withdrawal, across the major PD clusters (A, B, and C). Emerging findings from neuroimaging, genetic, pharmacological, and biomarker studies are integrated to illustrate how alterations in neurotransmitter signaling contribute to the pathophysiology of disorders such as borderline, antisocial, schizotypal, and avoidant personality disorders. This entry also critically evaluates the limitations of current models, emphasizing the need for multimodal and dimensional approaches that integrate neurotransmitter dynamics with genetic, developmental, and environmental factors. By elucidating the biochemical substrates of personality pathology, this entry aims to contribute to the development of more precise, neurobiologically informed interventions and to refine our understanding of the complex interplay between brain chemistry and personality structure.