Limes as a fruit crop are of great economic importance, key to Asian and South American cuisines and cultivated in nearly all tropical and subtropical regions of the world. Demand for limes is increasing, driven by World Health Organization recommendations. Pests and pathogens have significantly reduced global productivity, while changes in agronomic techniques aim to alleviate this stress. We present here a holistic examination of the major biotic (pests and pathogens) and abiotic (environment and socioeconomic) factors that presently limit global production of lime. The major producers of limes are India, China and Mexico, while loss of lime production in the United States from 2006 has led many countries in the Western Hemisphere (Mexico, Costa Rica and Brazil) to export primarily to the USA. The most widespread invertebrate pests of lime are Toxoptera citricida and Scirtothrips citri. Another insect, Diaphorina citri, vectors both Huanglongbing (HLB) and Witches Broom of Lime, which are particularly destructive diseases. Developing agronomic techniques focus on production of resistant and pathogen-free planting materials and control of insect vectors. HLB infects citrus in nearly all growing regions, and has been particularly devastating in Asian citrus. Meanwhile, Citrus tristeza virus has infected over 100 million citrus trees, mainly in the Americas and Mediterranean. Currently, Witches Broom Disease of Lime is localised to the Middle East, but recently it has been detected in South America. The range of its vectors (D. citri and Hishimonus phycitis) further raises concerns about the potential spread of this disease. Abiotic threats to lime production are also a significant concern; key areas of lime production such as Mexico, India and the Middle East suffer from increasing water stress and high soil salinity, which combined with invasive pests and pathogens, may eliminate lime production in these areas. To ensure future security in lime production, policy makers, researchers and growers will need to examine the potential of more resistant lime cultivars and establish novel areas of cultivation.