ω-Conotoxins are an interesting class of naturally occurring peptides that induce dramatic effects on the central nervous system (CNS). They have been shown to interfere with the normal function of neuronal calcium channels and can act as non-addictive analgesics. The usual problems associated with the delivery of peptidic therapeutics have led to efforts to produce non-peptidic mimetics of ω-conotoxins. Identification of the key amino-acid residues responsible for the physiological effects of the ω-conotoxins MVIIA and GVIA has allowed the design and synthesis of compounds that bind to neuronal calcium channels at low micromolar concentrations. These mimics bear the side chains of three amino acids that project from central scaffolds in similar ways to critical side chains of the conotoxins they simulate. Several useful leads have been identified, some of which show selectivity for N-type calcium channels.