We investigated the activity of the tuberculosis drug SQ109 against 16 fungal pathogens: , , , , , , , , , , spp., spp., spp., spp., and . MIC values varied widely (125 ng/mL to >64 μg/mL) but in many cases we found promising (MIC ∼ 4 μg/mL) activity as well as MFC/MIC ratios of ∼ 2. SQ109 metabolites were inactive. The activity of 12 analogs of SQ109 against correlated with protonophore uncoupling activity, suggesting mitochondrial targeting, consistent with the observation that growth inhibition was rescued by agents which inhibit ROS species accumulation. SQ109 disrupted H/Ca homeostasis in vacuoles, and there was synergy (FICI ∼ 0.26) with pitavastatin, indicating involvement of isoprenoid biosynthesis pathway inhibition. SQ109 is, therefore, a potential antifungal agent with multitarget activity.