Desert truffles are edible hypogeous (forming fruit bodies below ground) fungi that grow in semi-arid and arid areas. They are highly valued for both their culinary and medicinal properties in the Mediterranean basin, the Middle East and the Gulf areas. Desert truffles form mycorrhizae mostly with plants belonging to the Cistaceae family, mainly with Helianthemum species. These truffles are still, usually, collected from the wild, but loss of habitats due to urbanization, desertification, intensive agriculture and global warming, along with an urgent need to develop new crops adapted to arid conditions, are currently hastening efforts towards their domestication. Here, we sum up the successful research leading to cultivation of this crop, based on plots that were established in sandy to silt soils with high pH values and low mineral contents. We report suitable methods for production of mycorrhized seedlings and preferred planting methods. We found that under natural conditions yields are affected by water availability, so irrigation regimes to ensure good yields were sought. Although good yields were indeed obtained in some years, fluctuations in yields over the years were significant; the reasons for this are not entirely clear and are currently under study. This crop is particularly well suited to relatively marginal conditions but prospects for establishment of desert truffles as a niche crop for arid and semi-arid areas depend on further improvements in yields.