Among the microanalytical techniques, electron probe microanalysis (EPMA) is one of the most powerful. Its performances can be used to provide an accurate characterization. In the present article the differences between the EPMA of highly irradiated materials and standard EPMA are highlighted. It focuses on the shielded EPMA specificities. Then, the article presents the difficulties encountered during the sample preparation and the analysis (mainly due to the radioactive background). In spite of these difficulties, some valuable results can be provided by a shielded EPMA on the in-pile behavior of nuclear irradiated fuel. Some results of specific examples analyzed by EPMA in nuclear fuel research are presented.