Fruits are increasingly recognized as an important part of a healthy diet. Fruit crops represent a wide range of woody perennial species grown in orchards. Water availability is a primary environmental factor limiting fruit crop growth and productivity. Erratic rainfall patterns and increased temperatures due to climate change are likely to increase the duration of droughts. This review aims to highlight the different mechanisms by which fruit crops respond to water stress deficits. Emphasis is placed on physiological, genetic and epigenetic determinants of stress response in fruit crops. These findings can contribute to a deeper understanding of the underlying effects of drought. We also describe new research opportunities made possible by the increasing availability of population-level genomic data from the field, including genome-wide association studies (GWAS) and high-throughput phenotyping.