L-asparaginase is one of the protein drugs for countering leukemia and lymphoma. A major challenge in the therapeutic potential of the enzyme is its immunogenicity, low-plasma half-life and glutaminase activity that are found to be the reasons for toxicities attributed to asparaginase therapy. For addressing these challenges, several research and developmental activities are going on throughout the world for an effective drug delivery for treatment of cancer. Hence there is an urgent need for the development of asparaginase with improved properties for efficient drug delivery. The strategies selected should be economically viable to ensure the availability of the drug at low cost. The current review addresses various strategies adopted for the production of asparaginase from different sources, approaches for increasing the therapeutic efficiency of the protein and new drug delivery systems for L-asparaginase. (C) 2017 Published by Elsevier Ltd.