Neurodegenerative diseases represent one of the most devastating types of diseases in older populations in our time. Significant efforts have been made over the last 20 years to understand the molecular, biochemical, and physiological alterations underlying these diseases. However, in most cases, little is known about their pathological mechanisms due to their high complexity and involvement of a multiplicity of cellular pathways. To gain insight into this group of disorders and to devise potential therapeutic approaches, cellular and animal models of neurodegenerative proteinopathies have been created. Among them, the yeast Saccharomyces cerevisiae has been one of the most popular model organisms due to the degree of conservation of many biological pathways from yeast to human as well as its ease of use. Here, we describe how to create yeast models of neurodegenerative proteinopathies by ectopic expression of human proteins and how to perform a basic characterization of these models by analyzing cellular toxicity and protein aggregation.