This chapter provides an overview concerning the historical development of consultation-liaison psychiatry (CLP) and details the meaning of consultation and liaison activity. The procedure of consultation is detailed. Several assessment tools that support clinical investigation are presented and discussed. Specifically, the assessment of personality traits, anxiety and depressive symptoms, and other psychological factors are addressed. As far as clinical research is considered, two topics are presented: CLP within the psycho-neuro-endocrine-immune perspective and CLP in the field of transplants. Finally, special attention is dedicated to the impact of CLP on health care budgets and to the role played by CLP in end-of-life care. Several skills are required in the field of CLP. Some are general (e.g., assessment of psychiatric diagnosis and medical-psychiatric comorbidity, use of psychopharmacological treatments, etc.); others are specific to the setting (e.g., transplantation, end-of-life-care, etc.). Once acquired, both general and specific skills may be implemented in psychiatric settings other than the CLP, thus representing professional assets potentially useful in all psychiatric settings. Therefore, CLP should be considered not only as a subspecialty of psychiatry, but also as a forma mentis, a professional attitude that the psychiatrist may implement in several psychiatric settings.