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Parenteral amphotericin B has been considered as first-line therapy in the treatment of systemic fungal and parasitic infections, however its use has been associated with a number of limitations including affordability, accessibility, and an array of systemic toxicities. Until very recently, it has been very challenging to develop a bioavailable formulation of amphotericin B due to its physical chemical properties, limited water and lipid solubility, and poor absorption. This perspective reviews several novel oral Amphotericin B formulations under development that are attempting to overcome these limitations.