The yeast Saccharomyces cerevisiae has been used to develop a wide range of highly tractable living models of the major human neurodegenerative diseases. Yet even though this microorganism lacks neuron-specific structures and processes, these models have provided new insights into the underlying disease mechanisms. Furthermore, they have allowed new therapeutic targets to be identified as well as providing a means of identifying potential therapeutic agents using high throughput cell-based screens. In this article, the benefits and limitations of S. cerevisiae-based neurodegenerative disease models are explored. Consideration is also given to future opportunities the exploitation of these models present, including the use of other yeast species such as Schizosaccharomyces pombe.