Inflammation is a general term used to describe various pathological processes with diverse causes that can include infection, trauma, or an autoimmune response. Due to its many causes, the inflammatory response involves multiple and varied mediators, including vasoactive amines, free radicals, and both lipidic and peptidic mediators. Medicinal plants and the compounds derived from them are a good source of new and specific inhibitors of the inflammatory process. The past decade has witnessed many important discoveries in this field, with new findings challenging the more traditional views of pharmacologists. Various studies, for example, have demonstrated the positive effects of plant-derived phenolics, which act as anti-oxidants, free radical scavengers, and inhibitors of nitric-oxide synthase, cyclooxygenase, and lipoxygenase. The anti-inflammatory activity of chalcones has been correlated with the induction of heme oxygenase-1 while phlorotannins have been found to inhibit matrix metalloproteinase, which is implicated in arthritis, chronic inflammation, and wrinkle formation. Sesquiterpene lactones have been studied as inhibitors of NF-kappaB activity and the relationship between their chemical structure and pharmacological activity has been clearly established. Recently, cucurbitacins have been described as inhibitors of JAK -STAT and NF-AT functions related to inflammation; they were also found to induce apoptosis of cells involved in the inflammatory response. This review focuses mainly on the effects of natural products on transcription factors, which are the most promising targets for designing new active drugs against inflammation and cancer.