Asparaginase is one of the main drugs used to treat acute lymphoblastic leukemia and certain non-Hodgkin lymphomas. The drug is a bacterial product, and this results in differences in activity, efficacy, and side effects among the various marketed products. Native products originate from either Escherichia coli or Erwinia chrysanthemi. Currently a new product, PEG-asparaginase, is on the market. Recombinant asparaginases will be entering the market in a few years, and development of the incorporation of asparaginase in erythrocytes is progressing. This article reviews the available data on the various asparaginases and current developments. Differences between the various preparations are discussed in relation to pharmacokinetics, i.e. the short half-life of Erwinia preparations and prolonged activity of PEG-asparaginase. Uncertainties in relation to antibody formation and batch related differences of the newer products are discussed. The adverse effects related to origin of a product, mode of action, and antibody formation are also discussed.