Abstract
Azole antifungals are essential for controlling fungal diseases in medicine, veterinary care and agriculture. However, extensive cross-sector use has accelerated the emergence of resistant fungal pathogens, threatening human health, food security and ecosystem stability. This Review examines the dual role of azoles as life-saving therapeutics and drivers of antifungal resistance. We outline their development, mechanisms of action and applications across sectors, and highlight environmental and evolutionary pressures shaping resistance. Integrating perspectives from microbiology, agriculture and public health, we argue that coordinated One Health stewardship and sustainable antifungal strategies are urgently needed to preserve the efficacy of these critical compounds.