Amphotericin B is a natural polyene macrolide derived from Streptomyces nodosus and has emerged as a versatile therapeutic agent with significant implications in the management of systemic fungal infections and tropical dermatoses like leishmaniasis. Amphotericin B has a unique mechanism of action that includes sequestration of cholesterol and peroxidation of lipids in fungal and protozoal cells. Besides, it also facilitates immune modulation. Yet currently, challenges remain in establishing standardized treatment protocols with amphotericin B, with the need of randomized controlled trials to confirm the same.