The inducible transcription factor nuclear factor-kappaB (NF-kappaB) plays an important role in the regulation of immune, inflammatory and carcinogenic responses. While normal NF-kappaB activation is necessary for cell survival and immunity, deregulated NF-kappaB expression is a characteristic phenomenon in cancer development, as well as in several inflammatory diseases. Hence, NF-kappaB has become a major target in drug discovery, and several natural and synthetic compounds have been investigated for their potential to inhibit NF-kappaB. Here, we discuss the applications of marine natural products, in particular, as novel, potent NF-kappaB inhibitors. With the oceans covering two-thirds of the Earth's surface, and with the uniqueness of the environmental properties of marine habitats, it is easily understandable that organisms thriving in the oceans constitute a rich source of chemically unique and biomedically powerful secondary metabolites. Since the early 1960s, significant effort has been placed on the pharmacological evaluation of marine secondary metabolites. Noteworthy achievements of this field of biomedically guided marine exploration, a scientific endeavour often referred to as the search for "Drugs from the Sea", include the discovery of numerous potent anti-cancer, anti-inflammatory, antimicrobial, and analgesic compounds. The chemical characteristics and molecular targets of marine NF-kappaB inhibitors discovered to date are presented and discussed in the context of marine chemical ecology.