The Great Barrier Reef houses an amazing diversity of species. In a highly competitive environment many of these species have evolved defensive and/or prey-capture strategies that entail the use of potent bioactive compounds. Increasingly, many of these compounds have been found to be novel either on the basis of their structures, gene/protein sequences, or pharmacological profiles. As such they comprise a rich source of lead molecules for drug development. Among the species which inhabit the Great Barrier Reef and tropical waters around Australia are the Conidae. The Conidae (cone snails) have been studied for three centuries but only more recently was the pharmacology of their venoms investigated. Pioneering work by Robert Endean in the 1960s and 1970s at the University of Queensland on whole venom and since the 1980s by Baldomero Olivera at the University of Utah on isolated venom components (conotoxins) confirmed the potential of this rich new source of bioactive molecules. Endean’s efforts were focussed on whole venom from some 40 species of Conus,[1] and he confirmed earlier observations of selective phyla toxicity and demonstrated the presence of a number of selective and potent neuromuscular inhibitors from fish-eating species. This laid the foundation for Olivera’s discoveries on many individual venom components.[2] Since the early 1990s, Alewood and Lewis have led a multidisciplinary team of chemists, pharmacologists, molecular biologist, and structural biologists which has focussed on developing a better understanding of the structure–function relationships of the conotoxins with their receptors. The Conidae are carnivorous molluscs which comprise some 500 species worldwide (approximately 130 species in Australian waters) and prey predominantly on fish, molluscs, and worms. Their hunting strategy involves the delivery of a complex venom via a harpoon-like apparatus (Fig. 1). The venom is produced within the duct by specific cells and pumped towards the radula sack by a pump (or bulb).[3] The extendable proboscis holds the radula tooth ready to inject into the prey. During the process typically 20–50 µL is injected [4] and another radula is loaded for further use. This allows larger prey to be quickly immobilized. Analysis of the whole venom by liquid chromatography–mass spectrometry