Altered regulation of copper (Cu) homeostasis may contribute to the development of many pathologies, such as metabolic, cardiovascular, neurodegenerative and cancerous diseases. Cu serum concentrations are strictly related to oxidative stress. During the past decade, it has been well demonstrated that even marginal deficits of this element contribute to development and progression of a number of chronic diseases. On the other hand, an excess of Cu may become a potent oxidant causing the generation of reactive oxygen species (ROS) and leading to the formation of macromolecules dangerous to health. In this review we will describe several chronic inflammatory diseases pathogenically related to the alteration of serum copper levels. Some considerations on present and future perspectives for use of natural antioxidants as effective drugs for the treatment of chronic diseases will be made to shed a glimmer of light on some of the mechanisms employed by natural antioxidants in controlling the distribution and concentration of biometals.