Actinides, such as uranium, plutonium, or americium, are radioactive metals with no natural biological function. However, these elements are strongly retained by most organisms and can be extremely toxic due to their radioactive and chemical properties. In the event of an accidental or ill-intentional release of nuclear material into the environment, these radionuclides pose a severe health risk as contaminants. The only practical therapy to reduce the dramatic health consequences of internal actinide contamination is treatment with chelating agents that form excretable complexes, although the actinides are among the most intractable radionuclides to decorporate. In the last few years, a sense of urgency and a renewed interest in the study of actinide chemistry and biology have emerged, as threats of nuclear terrorism have become more plausible, and the risk of environmental contamination and human exposure to radioisotopes consequently increased. This chapter discusses available methods and recent progress in the development of new strategies for the chelation of actinides.