This concept paper, discusses the challenges and opportunities for an extractive chromatographic process for the separation of fission products and minor actinides from uranium and plutonium isotopes in irradiated nuclear fuel. The paper highlights the constraints of the PUREX process, a process that is universally accepted for reprocessing of spent nuclear fuel now and for GEN IV reactor systems. It also identifies the challenges that a new separation process would have to overcome to dislodge its acceptance by both the operators and regulators. Although the concept of using a chromatography technique for this separation is challenging, recent developments of continuous chromatography such as simulated moving bed (SMB) and/or continuous annular chromatography (CAC) provides a degree of encouragement. Equally the development of new stationary phases in particular inorganic exchangers, many of which have not been examined for this application enhances confidence that an alternative to the PUREX process is possible.