Models have been developed and utilized to examine the conditions necessary for attaining tritium fuel self-sufficiency in fusion reactors. Results show that these conditions define important limits on the parameter space in which the plasma and various reactor components have to operate. In addition, these conditions indicate preference for some material, design and technology choices. Results on conditions of fuel self-sufficiency can be used to guide experimental and analytical R&D efforts not only in neutronics, but also in a number of physics and technology areas.