Great number of molecular structures operating in rheumatoid arthritis (RA) present the evolutionary events in biology. Genesis of RA is closely linked to susceptibility genes and environmentals factors. The latter are modifying agents of genotype and signals initiating the disease. Inflammation exhibits very complex system in term of cooperation between cells – genes – molecules. The signal transduction cascade is followed by “unformed biological state” (Fig. 1). The crossing of border line in terms of homeostasis produces complex inflammatory events. The natural defense mechanisms are ineffective in protecting us from the disease. Modifying drugs, including biological agents, suppress the hyperactivity of cells, blocking “immunologic irritation”.