Global protein expression analysis, known as proteomics, has emerged as a novel scientific technology currently successfully applied to several fields of medicine including cancer and transplantation. Thereby, a thorough exploration of the pathogenic mechanisms and a better understanding of the pathophysiology of diseases as well as identification of diagnostic biomarkers have been achieved. In this paper, we outline the basic principles and potential applications of this promising tool in bariatric surgery where proteomics might hold great potential for new insights into diagnostic and therapeutic decision making based on improved knowledge of metabolic regulations pre- and postsurgical interventions in morbidly obese patients.