Inflammation is a vascular and cellular immune response that helps to eliminate pathogenic intruding various outfits. The inflammatory response is mediated by several cellular and humoral components and is principally controlled by several genes encoding pro-inflammatory (TNF- , IL-1beta, and IL-6) and anti-inflammatory (IL-10, arginase-1, and TGF-beta) mediators. This book enumerates a novel approach to use the nucleotide and amino acid sequences of the inflammation-inducing genes of various organisms of the animal kingdom to understand their phylogeny as well as the pattern of sequence divergence. The evolutionary impact on the structure-function relationships of the inflammatory mediators has been demonstrated by analyzing the protein structures to find out the biochemical and molecular physiology insights to explore the molecular under which they function.