Gamma rays generated in nuclear reactions have been used on the Joint European Torus (JET) for more than a quarter of a century to study the main mechanisms of fast-ion slowing down, redistribution as well as for the development of optimal plasma scenarios with auxiliary plasma heating. In future deuterium–tritium (D–T) fusion machines, γ-ray measurements, as well as neutron diagnostics, are amongst a very restricted set of plasma diagnostics that will be practical by virtue of their tolerance to the harsh radiation environments they will be required to work within. In this paper, we propose various applications using γ-ray diagnostics during all reactor exploitation phases, from the no-/low-activation to the burning D–T plasmas, for the setup of plasma discharges, characterisation of the auxiliary plasma heating, and development of optimal deuterium and D–T plasma scenarios. Possibilities of γ-ray diagnostics for α-particle studies in D–T and low-activation plasmas are comprehensively discussed. Nuclear reactions generating γ-rays, which are suitable for measurements in fusion devices, have been selected and recommendations for their usage based on their previous experience on JET are given. This paper provides insights for the design and modelling of γ-ray diagnostic systems, as well as testing them in currently working fusion devices before their use in burning plasma machines.