The influenza virus neuraminidase (NA) is important in the pathogenesis of infection and, thus, is an attractive target for agents used in the treatment and prophylaxis of influenza. This article describes preclinical and early clinical data related to RWJ–270201 (BCX–1812), a novel, orally active NA inhibitor that was rationally designed for having potent and selective activity against influenza A and B viruses. RWJ–270201 is a unique NA inhibitor with a cyclopentane ring structure and high selectivity for the influenza NA. RWJ–270201 has efficacy comparable to or better than earlier NA inhibitors against a wide range of influenza A and B isolates, including recently emerged and avian strains, both in vitro and in a lethal murine model of influenza. Based on the high selectivity and efficacy of RWJ–270201 against both type A and B influenza strains in preclinical studies as well as murine pharmacodynamic studies supporting the potential for once–daily administration, clinical trials were initiated in order to determine the tolerability and antiviral activity of RWJ–270201 in humans. To date, clinical studies have indicated that RWJ–270201 is well tolerated and has antiviral activity in human experimental influenza models when administered orally once daily.