Selenium (Se) is an essential micronutrient for human health, but its deficiency may affect at least one billion people worldwide. Plants and plant-derived products transfer the soil-uptaken Se to humans through the food chain, which is hardly enough when soils have been always poor or already exhausted in bioavailable Se species. Other than agronomic approaches for enhancing Se levels in cereals, such as soil and foliar supplements, seed enrichment may be viewed as an alternative Se-biofortification technique. This study addresses the protocol for preparing Se-enriched wheat seeds, with the specific purpose of optimizing the administration of Se to the seeds prior to sowing. The first step was to soak an amount of bread-wheat seeds in an active Se solution, made with irradiated [Na2O4Se], and then monitoring 75Se in periodically-retrieved samples from that original amount. To avoid losing Se to soil (after sowing), and, especially, to ensure that Se gets really absorbed into the seeds—and not just adsorbed onto them—the washing time of the seeds should be optimized as well. This was carried out by washing Se-treated seeds several times, until no significant amount of the radiotracer could be detected in the washing water. In what concerns the full optimization procedure, the overall results of the present study point to an optimum time of 48 h for soaking and 24 h for washing.