A large number of materials exist which have been labeled as low activation structural materials (LAM). Most often, these materials have been designed in order to substitute-out or completely remove elements that become activated and contribute signi cantly to shut-down activity after being irradiated by neutrons in a reactor environment. To date, one of the fundamental principles from which LAMs have been developed is that natural elemental compositions are the building blocks of LAMs. Thus, elements such as Co, Al, Ni, Mo, Nb, N and Cu that produce long-lived decay products are signi cantly reduced or removed from the LAM composition. These elements have an important part to play in the composition of steels and the removal/substitution can have a negative impact on materials properties such as yield stress and fracture toughness. This paper looks in more detail at whether using isotopic selection of the more mechanically desirable, but prohibited due to activation, elements can improve matters. In particular, this paper focuses on the activation of Eurofer. Carefully chosen isotopically enriched elements, which are normally considered to be on the prohibited element list, are added to EUROFER steel as potential alloying elements. The EUROFER activation results show that some prohibited elements can be used as alloying elements in LAM steels, providing the selected isotopes do not have a signi cant impact on waste disposal rating or shut-down dose. The economic implications of isotopically enriching elements and the potential implications for decommissioning are considered. It is shown that the addition of molybdenum and nickel in small concentrations (< 2 % mass) could have the potential to increase availability to such an extent that the capital investment associated with isotope enrichment is negated and pro ts from electricity sale increased. Another important issue for materials exposed to neutron irradiation is the production of gases, in particular helium, as a result of nuclear interactions. Helium accumulation in materials can cause embrittlement and so mitigating the rate of production is an important consideration when selecting materials. The second part of this paper considers whether helium production can be reduced in CuCrZr by isotopic tailoring. CuCrZr is a candidate bonding material for tungsten at rst wall locations, however it su ers from degradation due to helium production. Inventory calculations show that isotopically enriching the copper, in CuCrZr, can reduce helium production by approximately 50%. However, cost-bene t analysis suggests that the cost of enriching copper is not cost-e ective due to the high price of electromagnetic enrichment that is required for copper.