Antiviral chemotherapy is based on the selective inhibition of intracellular virus multiplication. Inhibitors of viral DNA polymerases perfectly exemplifies this mode of action. In spite of their selectivity, some of these drugs are cytotoxic and all remain unefficient against latent viruses. Evaluation of antiviral activity requires in vitro sensitivity tests, in vivo studies on animals and virological analyses during clinical trials. This evaluation needs well standardized assays. The emergence of in vitro resistance reflects the occurrence of mutations regarding target enzymes. Clinical significance of antiviral drug resistance needs to be assessed in many circumstances, even if its association with immunodeficiency often leads to a clear therapeutic failure. Further developments will include the synthesis of novel inhibitors, study of drug associations and improvement of virological diagnosis techniques relevant to therapy.