For several decades, researchers have been investigating the relations between the consumption of Maillard reaction products (MRPs) and biological activities, whether harmful or beneficial. Interest in this area is growing because the intake of these compounds has increased in parallel with the consumption of thermally processed foods. MRPs are bioavailable to some degree and, although there is little consensus about possible harmful effects or pathways of action, there are pathological implications regarding the progress and development of various degenerative disorders. Besides these considerations, it has been reported that some MRPs, particularly melanoidins, have beneficial effects as antioxidant, anti-inflammatory or anti-aging factors, among others. Some interesting aspects of this dual nature of MRPs are addressed in the present review. In this context, it is difficult to draw firm conclusions about the physiological consequences resulting from MRPs intake, due to the diversity of compounds formed in the different food matrixes. Maintaining a balanced and varied diet, not only in the food consumed but also in how it is processed, is increasingly viewed as the best strategy to limit the negative effects and to preserve the positive actions of dietary MRPs. Much remains to be done to elucidate the chemical structures of these compounds and to relate it to specific physiologic actions. For that purpose, setting the chromatographic determinations as the most reliable analytical tools to measure them in foods and biological tissues/fluids seems essential. Moreover,designing more realistic and better controlled clinical studies, based on the real diet of the population, will be the only method to perform an effective health-risk assessment of MRPs consumption.