Fungal infections are a public health problem on the global scene, which is worsening with the increasing resistance to antifungal drugs and the contemporary climate change scenario. These infections continue to be underestimated, with insufficient economic efforts and few classes of effective antifungal drugs, with increasing reports of resistance by fungi such as the genera Aspergillus, Candida, Cryptococcus, Fusarium, Histoplasma, and Rhodotorula, among others. In addition, many mycoses are treated with drugs for an extended period. The need for new antifungal therapies requires the investigation of alternative routes, using natural sources of antifungals and which are economically viable and sustainable. In this context, despite its geographic isolation and peculiar climatic conditions, Antarctica is home to a fungal community that produces antifungal drugs, including Aspergillus sydowii (versicone A), Purpureocillium lilacinum, Penicillium, Pseudogymnoascus, Aspergillus flavus, Oidiodendron truncatum (quetracin), Chrysosporium sp., Cladosporium sp., Acrostalagmus luteoalbus (luteoalbusin A and T988 C), Geomyces sp. (Geomycin B), Penicillium nalgiovense Laxa (amphotericin B), Pseudogymnoascus, Guehomyces pullulans, Metschnikowia australis, Cladosporium sp., Trichoderma polysporum, and Penicillium chrysogenum. In general, fungal extracts have shown activity against pathogenic fungi of global importance, such as Candida albicans, Fusarium oxysporum, Paracoccidioides brasiliensis, Aspergillus fumigatus, Candida krusei, Cladosporium sphaerospermum, and Cryptococcus neoformans. More detailed studies on the chemical characterization of the extracts, toxicity, and production optimization are relevant to elevate Antarctic fungi as an alternative antifungal therapy.