Psycho-emotional disorders such as depression and anxiety disorders are important modifiable risk factors for the development and complicated course of many common chronic non-communicable diseases. A particular feature of such comorbidity is the significant impact of psycho-emotional disorders on the motivation and adherence of patients to a healthy lifestyle and various therapy options, which increases the risks of complications and, as a consequence of this, the healthcare expenditures. The topicality of the issues of screening and management of psycho-emotional disorders in the general practitioner practice is caused, on the one hand, by high rate of these disorders in patients with chronic non-communicable diseases, deterioration in quality of life and an increase in adverse outcomes, and on the other hand, inadequate awareness of the possibilities to manage the psycho-emotional state of patients with comorbidities. The therapy for psycho-emotional disorders includes both drug and non-drug methods, however, the effectiveness of such therapy in relation to the clinical course and prognosis in patients with different comorbidities is not the same. This review presents the most common comorbidities of psycho-emotional disorders and somatic diseases in therapeutic practice. A buspirone and tofisopam therapy for psycho-emotional disorders in patients with various comorbidities was discussed. The efficacy and safety of tofisopam and buspirone have been studied in numerous studies in patients with chronic diseases and a wide range of anxiety disorders, including a long-term administration.