Several isotopes are examined as alternatives to 238Pu that is traditionally used in radioisotope thermoelectric generators (RTGs) and heating units (RHUs). The radioisotopes discussed include 241Am, 208Po, 210Po, and 90Sr. The aim of this study is to facilitate the design of an RTG with a minimal radiation dose rate and mass including any required shielding. Applications of interest are primarily space and planetary exploration. In order to evaluate the properties of the alternative radioisotopes a Monte Carlo model was developed to examine the radiation protection aspect of the study. The thermodynamics of the power generation process is examined and possible materials for the housing and encapsulation of the radioisotopes are proposed. In this study we also present a historical review of radioisotope thermoelectric generators (RTGs) and the thermoelectric conversion mechanism in order to provide a direct comparison with the performance of our proposed alternative isotope systems.