Technical Abstract: Many yeast pathogens of humans have become resistant to currently available drugs. Certain types of compounds can increase efficacy of antimycotic drugs through a process termed chemosensitization. Chemosensitizing efficacy was determined in Candida albicans, C. krusei, C. tropicalis and Cryptococcus neoformans, yeasts that are causative agents of human candidasis or cryptococcosis. We compared chemosensitizing activities of four redox-active benzaldehydes, i.e., two dihydroxybenzaldehydes (DHBAs) [2,3-dihydroxybenzaldehyde (2,3-DHBA), 2,5-dihydroxybenzaldehyde (2,5-DHBA)] and two nonhydroxylated benzaldehydes (non-DHBAs) [trans-cinnamaldehyde, 3,5-dimethoxybenzaldehyde (3,5-DMBA)], to the preferred commercial drug for treating these diseases, amphotericin B (AMB). In most yeast pathogens tested, co-application of either of the DHBAs enhanced antifungal activity of AMB, as measured by lower minimum inhibitory concentrations (MICs) and/or minimum fungicidal concentrations (MFCs). With non-DHBAs, certain levels of chemosensitizing activity were detected with cinnamaldehyde (for MFCs). However, no chemosensitization was achieved by 3,5-DMBA in any of the yeasts tested. This lack of chemosensitization was mainly due to hypertolerance of yeast strains to 3,5-DMBA. Results show certain DHBAs are potent chemosensitizing agents to AMB in Candida and Cryptococcus. 2,3-DHBA showed higher antifungal activity than 2,5-DHBA (i.e., structure-activity relationship). Also, the two DHBAs possessed much higher chemosensitizing potency than the non-DHBAs tested. DHBAs may exert their chemosensitizing activity to AMB by targeting mitochondrial superoxide dismutase (Mn-SOD). DHBAs could serve as effective chemosensitizers to AMB for improved chemotherapeutic treatment of candidiasis and cryptococcosis.