The correlation between the production of IL-8, along with many chemokines and inflammatory diseases, has been well documented. Therefore, modulation of IL-8 production is a viable approach to drug discovery for the treament of inflammatory diseases. Two general approaches to regulate IL-8 production are most prevalent. One is direct inhibition of IL-8 receptors, CXCR1 and/or CXCR2. The other is downstream regulation of IL-8 production via inhibition of p38 kinase. This review accounts the patent literature published between 1998 and 2001, covering small molecule IL-8 modulators using both approaches.