Introduction: This theoretical narrative perspective will focus on pointing out the psychobiological factors which are involved in the genesis and treatment of personality prominent traits and disorders. Material and method: After a suitable search, mainly in PubMed and Psyc Info Journal databases, the number of selected quality publications is n= 95. The reduced sample sizes and numerous research designs that are merely exploratory or observational are its main limitations. Results and discussion: Regarding the psychopathology of personality neurodevelopment, environmental and genetic factors as well as neurotransmitter impairments are confirmed to be involved. Of interest are the endophenotypic perspective, endocannabinoid system and hypothalamus-regulated endocrine axes, among others. Neuroimmunology predicts important clinical and therapeutic innovations, but they are not a reality yet. It has been suggested that only with psychological interventions of various types is there symptomatic improvement as well as a favourable effect on stress-related epigenetic mechanisms. Psychopharmacotherapy continues to be useful, mainly off-label, with antipsychotics, anticonvulsants and opioid antagonists. Conclusions: In the absence of support from convincing qualified evidence, both users and health physicians usually prefer any type of psychological intervention to tackle complex personality clinical dysfunctions, without excluding complementary psychopharmacotherapy.