Radiation sterilization has been considered a mass decontamination technique for biodegradable cultural heritage (CH) since its widespread application in the medical field. Initial experiments have revealed advantages, for example, efficiency and effectiveness, but also disadvantages, namely “side effects” concerning CH materials. More than 50 years later, the adequacy of ionizing radiation for some CH artefacts is still the subject of discussion. The main reason why is that science and industry are not yet able to provide a more efficient technique for treating mass decontamination. For wooden items, there is general agreement that the irradiation dose required for insect eradication is not damaging, even in the case of polychromed wood. For cellulose pulp (paper), there is a reduction in polymerization degree (DP) at the high doses necessary to stop the attack of fungi, but this should be considered taking into account the purpose of the treatment. Emergency or rescue treatments are necessary to mitigate the consequences of accidents or improper storage conditions. In some cases (archives), the value of written information is greater than the historical value of the paper support. For other materials, namely textiles, leather and parchment, less research has been published on the effect of ionizing radiation treatment. As a general rule, irradiation is not necessary when only a few CH elements are present that are affected by biological contamination since restorers can solve the problem by classical means. The need for radiation treatment arises when large collections (hundreds, thousands or even more elements) are heavily affected by the biological attack. In Romania, the IRASM gamma irradiator of IFIN-HH is receiving an increasing number of requests for CH treatment, mainly due to an intensive research programme concerning this topic and close liaison with CH owners or administrators. Besides reviewing the scientific results obtained in Romania and abroad, this paper presents some examples from experiences in Romania.