Given that the long-term medical management of HIV infection necessitates making best use of all available antiretrovirals, it is somewhat surprising that the nucleoside analogue reverse transcriptase inhibitor (NRTI) zalcitabine is less commonly used. This may be due to the potential for peripheral neuropathy (PN) which has been associated with the use of this drug. The perception that zalcitabine is poorly tolerated appears to have arisen largely from the results of early monotherapy trials in patients with AIDS and low CD4 cell counts. In contrast, results of more recent studies show that PN is relatively infrequent when zalcitabine is used in combination with other antiretrovirals in current treatment settings.