Renal transplantation is a well established treatment for end-stage renal disease, allowing most patients to return to a satisfactory quality of life. Studies have identified many problems that may affect adaptation to the transplanted condition and post-operative compliance. The psychological implications of transplantation have important consequences even on strictly physical aspects. Organ transplantation is very challenging for the patient and acts as an intense stressor stimulus to which the patient reacts with neurotransmitter and endocrine-metabolic changes. Transplantation can result in a psychosomatic crisis that requires the patient to mobilize all bio-psycho-social resources during the process of adaptation to the new foreign organ which may result in an alteration in self-representation and identity, with possible psychopathologic repercussions. These reactions are feasible in mental disorders, e.g., post-traumatic stress disorder, adjustment disorder, and psychosomatic disorders. In organ transplantation, the fruitful collaboration between professionals with diverse scientific expertise, calls for both a guarantee for mental health and greater effectiveness in challenging treatments for a viable association between patients, family members and doctors. Integrated and multidisciplinary care should include uniform criteria and procedures for standard assessments, for patient autonomy, adherence to therapy, new coping strategies and the adoption of more appropriate lifestyles.