Cidofovir is a cytidine nucleotide analogue recently licensed as an intravenous treatment for CMV retinitis in AIDS patients. Three controlled clinical trials have demonstrated efficacy of cidofovir for this indication, and have generated data useful as a guideline to prevent potential toxicity. Although de novo emergence of resistance to cidofovir has not been observed clinically in patients receiving cidofovir, cross-resistance to cidofovir in ganciclovir-resistant clinical DNA polymerase mutants has been identified. Cross-resistance of cidofovir and foscarnet has not been identified to date. A broad spectrum agent with in vitro activity against human herpesviruses, adenovirus, HPV, polyomaviruses and human poxviruses, cidofovir is under clinical investigation for a variety of potential applications. Examples include intravenous administration of cidofovir for treatment of progressive multifocal leukoencephalopathy and Kaposi's sarcoma, intraocular injection for treatment of CMV retinitis, intralesional injection for treatment of respiratory papillomatosis, topical application for treatment of molluscum contagiosum, anogenital condyloma acuminata, and recurrent genital herpes, and ophthalmic instillation for treatment of viral keratoconjunctivitis. 1997 by John Wiley & Sons, Ltd.