Antiretrovirals have progressively entered clinical practice since the discovery of the association between the acquired immunodeficiency syndrome (AIDS) and human immunodeficiency virus (HIV) infection. Among the classes of drugs which have shown efficacy against HIV, nucleoside-based reverse transcriptase inhibitors (NRTIs) have been extensively investigated in both their basic and therapeutic aspects. The basic mechanism of the effects of NRTIs relies on interaction with both viral and host cell functions. This implies that NRTIs could act not only by inhibiting viral genome replication, but also by interfering with some basic mechanism regulating cell growth and death. According to these characteristics, NRTIs might share several similarities with antineoplastic agents, including side effects. In this article, we have briefly reviewed the pharmacological activities of NRTIs in viral replication, neoplastic growth and cellular functions. These aspects might be involved both in the beneficial and adverse effects of NRTIs