Marine organisms have been increasingly regarded as excellent sources of new drugs for human therapeutics due to their remarkable chemistry, which, in turn, is reflected in their wide range of biological applications, including cancer, inflammation, infection, and pain. In the past 20 years, several new drugs have been discovered, some of them with novel pharmacological targets and the first sea-derived approved medicines are now paving their way into the market. In this chapter, we will focus on small-molecule drugs obtained from marine animals (sponges, gorgonians, mollusks, echinoderms) for the treatment of inflammation. The distribution of these compounds by different taxonomical families will be discussed, as well as the state-of-the-art regarding their structure–activity relationship. The most important chemical classes will be presented, such as terpenes, alkaloids, among others. The most important molecular targets, including phospholipase A2 (PLA2), cyclooxygenases (COXs), nitric oxide synthase (NOS), and NF-κB will be discussed.