Persian walnut (Juglans regia L.) is the only species of the genus Juglans widely cultivated for nut production. Over the last 20 years, global walnut production has grown by almost 250%, with China, the United States and Iran as leading producing countries. This enormous growth is mainly attributed to an increase in regular consumption of walnut due to its high nutritional value and numerous benefits to human health. Walnut breeding programmes are facing the challenge of increasing production sustainably because of climate change and human population growth. This chapter reviews recent efforts and achievements in ecologically and economically friendly walnut cultivation. The chapter describes different practices that have been applied in this direction, such as the development of new cultivars with genetic resistance to biotic and abiotic stresses, the identification of solutions for reducing input consumption, and the exploration and conservation of genetic diversity in walnut.