© 2019 Elsevier Inc. All rights reserved. Inflammation is a physiological homeostatic response of the innate system toward infectious and noninfectious agents. Acute inflammation is triggered by the immune system and initiates a cascade of various biochemical events in order to address and eliminate these external factors. The initiation and resolution of the inflammatory response involves the complex and coordinated expression of many factors, including cytokines, chemokines, growth factors, proteases, oxidative stress products, and lipid mediators. Persistent induction and dysregulation of inflammation can lead to the development of chronic inflammatory diseases (CID) and metabolic disorders such as obesity, diabetes, renal disorders, cancer, atherosclerosis, and cardiovascular diseases (CVD). Interestingly, in such pathological conditions, the common junctions of inflammatory mechanisms coexist, leading to comorbidities in such diseases. In this chapter, the most common proinflammatory mediators and pathways that play key roles in this inflammatory network are presented. Finally, the role of systemic inflammation in pathologies such as metabolic syndrome, obesity, diabetes, cancer, atherosclerosis, and CVD is summarized.