The current problems in controlling severe viral infections such as AIDS as well as the lack of effective and safe therapeutic measures for such diseases have caused interest in systems such as macromolecular prodrugs potentially able to solve heavier drawbacks of conventional antiviral therapy. This review focuses on various approaches proposed in the literature in this field. Neoglycoproteins and synthetic protein-like structure polymers have been mainly proposed. In the first group, the possibility of incorporating into the polymeric structures a determined amount of sugar molecules make them interesting candidates for targeting of infected blood cells. The conjugate of zidovudine (AZT) and an anti-transferrin receptor antibody OX-26 has been proposed for brain targeting. The conjugate of AZT with alpha,beta-poly(N-hydroxyethyl)-DL-aspartamide (PHEA) showed good release properties in a prolonged time.