Inflammation seems to be at the beginning of the majority of chronic diseases, and major efforts are dedicated to the development of anti-inflammatory drugs. Chronic inflammatory diseases, such as psoriatic arthritis, rheumatoid arthritis, inflammatory bowel disease and asthma, are diseases that affect a large segment of our population. Recent evidence suggests that even metabolic diseases, such as type 2 diabetes, and certain cardiovascular diseases, could also be considered to have an inflammatory origin. However, a chronic disorder that in its initial and even more advanced stages is often not life-threatening, presents a challenge for therapeutic intervention: companies have to develop drugs that are efficacious, relatively free of side effects, and can be used effectively for a long time. The identification of suitable targets, thus, depends on better understanding of the signaling pathways involved in the initiation and maintenance of inflammation. The availability of target validation technology, such as targeted mutagenesis in mice, gene silencing mediated by small interfering RNA and protein expression profiling in this context is of utmost importance. Here, we will focus on the latter two technologies.