The recent outbreaks of West Nile virus (WNV) and other emerging and re-emerging flaviviruses, have made prevention and treatment of flavivirus infections a global public health priority. No inhibitor is currently available for use as an antiflavivirus therapy. In this communication, I review (i) stages of flavivirus replication representing potential targets for antiviral drug discovery; (ii) strategies for identification of flavivirus inhibitors; and (iii) existing antiviral inhibitors reported to have anti-WNV or other antiflavivirus activities. Flaviviruses share conserved nucleotide elements and amino acid sequences, and have similar genome organization and replication strategies. As such, it is hoped that broad spectrum flavivirus inhibitors could be identified through screening of compound libraries.