The exposure of plants to drought conditions inhibits shoot growth, increases production of toxic reactive oxygen species (ROS), and negatively affects photosynthesis and carbohydrate metabolism. Drought susceptibility in potato impacts all stages of the crop, from emergence to tuber initiation. Although there have been various studies of the global changes in gene expression profiles during drought conditions in potatoes, few studies have been based on native potato species. Because of their high genetic diversity, native potatoes from the Andean regions of Peru, Ecuador and Bolivia, are well adapted to the harsh environmental conditions that prevail in the Andes, including drought. This makes them ideal candidates for gene expression studies associated with drought tolerance. The identification of drought tolerance traits and genes for potato will facilitate breeding for high yield stability under drought conditions. The first phase of this study consisted on a comparative RNA sequencing analysis between drought-tolerant and drought-susceptible native potato cultivars. During the second phase, a drought experiment with both tolerant and susceptible native potato species, using an aeroponics growth system was conducted. Selected drought-associated candidate genes from the RNA sequence analysis were used in primer design and quantitative RT-PCR analysis. Differential gene expression in tolerant vs. susceptible cultivars has been confirmed for two heat shock proteins and for a triacyl glycerol lipase. Additional candidate genes are being tested. In conclusion, native potatoes are providing important information on genes affected by drought conditions.