Nucleoside chemistry represents an important research area for drug discovery, as many nucleoside analogues are prominent drugs that have been widely applied in cancer and viral chemotherapy. However, the synthesis of modified nucleosides presents a major challenge. Most of the currently available methods require toxic, high-boiling solvents, long reaction times and tedious workup methods. The situation is further aggravated by the poor solubility of the nucleosides in common organic solvents. There is a constant effort to develop process chemistry in alternative media to limit the use of organic solvents that are hazardous to the environment and can be deleterious to human health. Ionic liquids (ILs) are ‘designer materials’ with unique physico-chemical properties. The methodologies utilizing ionic liquids for the synthesis of pharmaceutically important nucleoside analogues, including some antiviral drugs, are highly convenient and efficient. This article is focused on the recent developments made in nucleoside chemistry using ILs as a reaction medium.