Psychosomatic research has advanced over the past decades in dealing with complex biopsychosocial phenomena and may provide new effective modalities of patient care. Among psychosocial variables affecting individual vulnerability, course, and outcome of any medical disease, the role of chronic stress (allostatic load/overload) has emerged as a crucial factor. Assessment strategies include the Diagnostic Criteria for Psychosomatic Research. They are presented here in an updated version based on insights derived from studies carried out so far and encompass allostatic overload, type A behavior, alexithymia, the spectrum of maladaptive illness behavior, demoralization, irritable mood, and somatic symptoms secondary to a psychiatric disorder. Macroanalysis is a helpful tool for identifying the relationships between biological and psychosocial variables and the individual targets for medical intervention. The personalized and holistic approach to the patient includes integration of medical and psychological therapies in all phases of illness. In this respect, the development of a new psychotherapeutic modality, Well-Being Therapy, seems to be promising. The growth of subspecialties, such as psychooncology and psychodermatology, drives towards the multidisciplinary organization of health care to overcome artificial boundaries. There have been major transformations in health care needs in the past decades. From psychosomatic medicine, a land of innovative hypotheses and trends, many indications for changes in the current practice of medicine are now at hand. The aim of this critical review is to outline current and potential clinical applications of psychosomatic methods.