Nuclear power sources can be effectively employed to generate renewable energy as a counter to global reliance on fossil fuels and increasing energy demands. Nuclear radiation can be utilized in numerous ways to produce energy. Along with their use as fuel for nuclear power plants, the decay process of radioisotopes can also be used to create electrical energy. A radioisotope thermoelectric generator (RTG) is one such example, as it is tasked to convert the decay energy of radioisotopes into heat energy, which is later converted into electrical power using the Seebeck effect. Radioisotopes have high energy densities and certain isotopes can generate considerable heat energy for prolonged timescales. As such, RTGs have found applications in powering interplanetary exploration and interstellar space missions due to their long half-life. They are also commonly used in remote regions of the earth where frequent replacement, charging and maintenance of power sources is difficult. In this review, we will discuss the working principle and architecture of RTGs, challenges faced in further development and potential applications of this technology.