Inflammation is an important contributor to the development and progression of all human cancers. Inflammatory lipid metabolites, prostaglandins, formed from arachidonic acid by prostaglandin H synthases commonly called cyclooxygenases (COXs), bind to specific receptors that activate signaling pathways driving to the development and progression of tumors. Inhibitors of prostaglandin formation, COX inhibitors, including non-steroidal anti-inflammatory drugs (NSAIDs), are well documented agents that inhibit tumor growth and prevent tumor development specially due to long-term use. NSAIDs also alter gene expression independently of COX inhibition which also appear to contribute to the anti-tumorigenic activity of these drugs. In a dermatologic point of view, most investigations are oriented to improve the current knowledge related to the pathogenesis of malignant melanoma, a prevalent skin cancer characterized by a rapid progression with frequent metastases and a poor response to the different available treatments. In the present issue we review the role of inflammation in cutaneous malignant melanoma and its impact on cancer pathogenesis. This topic represents an exciting new area of research, and could potentially result in new targets for melanoma therapy in the future.