The opportunistic fungal pathogen Candida glabrata poses a clinical challenge in the successful treatment of invasive Candida infections, owing to its low inherent susceptibility toward azole antifungals and the recent acquisition of coresistance toward azole and echinocandin drugs. Compared to other prevalent Candida bloodstream pathogens, C. glabrata neither exhibits secreted proteolytic activity nor invokes a strong immune response in a variety of host cells and is less virulent. It also does not form true hyphae, and the success of C. glabrata, therefore, as a prevalent human fungal pathogen, appears to be built upon a distinct set of virulence attributes. The focus of this review is to outline, in brief, the interaction of C. glabrata with the host, deduced from the knowledge gained from different in vitro, ex vivo, and in vivo model systems. In addition, we briefly discuss the current antifungals, antifungal resistance mechanisms, and the development of new antifungal therapies, along with the available information on the host response. A detailed understanding of stresses, selection pressures and differential immune responses in the presence and absence of antifungals that C. glabrata encounters in varied niches of the host, is required to design effective antifungal therapy.