The aim of this study was to assess the impact of social and psychological factors on treatment adherence of patients with tuberculosis (TB). To this end a cross-sectional questionnaire-based study was conducted among TB patients in four Russian regions (Orel, Vladimir, Belgorod oblasts, and Republic of Mari-El) from 01/04/2004 to 31/03/2005. A total of 87 non-adherent and 1302 adherent patients were interviewed. Compared to adherents, non-adherents were significantly more likely to be male, unemployed, have a technical college education, have a history of imprisonment, have a negative emotional status, consider themselves “not sick”, not know the treatment period, have negative feelings and distrust for medical staff, not believe they will fully recover, and not want to continue treatment. Patients at highest risk for non-adherence should be identified at the start of treatment, and offered the services of a psychologist. A case management and patient-centered approach should be applied.