The rise of immunocompromised individuals in our society has provoked a significant emergence in the number of patients affected by opportunistic pathogenic yeast. The microorganisms with a major clinical incidence are species from the genera Candida (especially Candida albicans) and Cryptococcus (particularly Cryptococcus neoformans), although there has been a significant increase in other pathogenic yeasts, such as Trichosporon spp. and Rhodotorula spp. In addition, there are an increasing number of patients infected by yeasts that were not previously considered as pathogenic, such as Saccharomyces cerevisiae. The management of these infections is complicated and is highly dependent on the susceptibility profile not only of the species but also of the strain. The available antifungal compounds belong mainly to the polyene, azole and candin families, which show a distinct spectrum of activity. This review summarizes the current knowledge about the use of the main antifungals for treating infections caused by the yeast species with the most significant clinical relevance, including the susceptibility profiles exhibited by these species in vitro.