Efforts to develop new safer and more effective anti-inflammatory drugs are based on the improved understanding of the role of key mediators identified as the key culprits in this malady. Inhibitors, which specifically interfere with components of different intracellular signaling pathways or inhibit the activation of transcription factors responsible for the expression of disease, related genes might have applications as novel therapeutic agents in inflammation. In order to search new inhibitors of inflammatory signal transduction pathways, inducible reporter gene vectors are constructed containing the natural promoters of inflammatory genes (COX-2, iNOS, TNF-a) or using binding sites for defined transcription factors (NF-kB, AP-1, glucocorticoid receptor, STATs). Submerged cultures of bacteria and fungi are examined for the production of compounds, which inhibit the stimulus dependent expression of the reporter gene in various mammalian cells. Present day anti-inflammatory drug discovery is based on preliminary in vitro observations in a number of standard anti-inflammatory assays, in which the test compound produces unusually potent antagonism of inflammatory pathways such as the arachidonic acid pathways and some cytokine cascades. The effective candidate drug in in vitro tests is later tested in whole animal models of acute, sub acute and chronic inflammation.