and the molecular events responsible for converting a normally benign commensal into a highly pathogenic organism, which in systemic infections can produce 30-45% mortality, have not been fully elucidated [7; 8; 9; 10; 11]. Moreover, the therapeutic repertoire to treat systemic _Candida_ infections is limited [12]. There are four classes of antifungal agents used clinically, including polyenes (e.g., Amphotericin B), echinocandins (e.g., caspfungin), azoles (e.g., fluconazole) and nucleoside analogs (e.g., flucytosine) [13]. Amphotericin B (AmB) was utilized as an early therapeutic for _Candida_ infections and its derivatives remain among the most effective treatments for systemic disease [14; 15; 16]. For these reasons, AmB was chosen for analyses in the microgravity-associated susceptibility studies described herein. It has been proposed that AmB functions at the level of the cell membrane, where it interacts with the yeast-specific sterol, ergosterol, forming pores and compromising membrane integrity [13; 15]. In contrast, caspfungin (CAS) was used to evaluate the yeast response to an antifungal agent harboring a mechanism of action distinct from that of AmB. Caspofungin compromises cell wall formation by inhibiting (1-3)-\(\beta\)-D-glucan synthase [11]. _C. albicans_ is a dimorphic eukaryotic organism consisting of spherical yeast form cells and elongated filamentous cells and has been shown to respond to environmental stresses such as temperature, pH, and altered gas environments with physiological characteristics often associated with virulence [17; 18; 19; 20]. Indeed the extreme environment of microgravity presents a unique challenge for organisms that have evolved under normal gravity. Microgravity may provide novel environmental stress cues leading to physiological adaptations or may allow insights into molecular pathways otherwise masked by a gravity-based environment, such as that described for the Pseudomonas _Hfq_ pathway [21; 22]. Among the potential adaptations of interest are those properties of _C. albicans_, on both the single and multicellular level, that enable it to infect an immunocompromised host. A well-studied phenotypic transition in _C. albicans_ is filamentation, or hyphal/pseudohyphal formation, which can be induced by a variety of environmental conditions including temperature, pH, serum, elevated CO\({}_{2}\) and hypoxia [23; 24; 25]. The combination of filamentous and yeast form cells can also form biofilms, or multicellular communities, contributing to increased virulence and enhanced resistance to environmental insults. As such, _C. albicans_, particularly in community form, has been documented to have increased resistance to antifungal agents [4; 26; 27]. In short, this yeast is capable of altering its phenotype in a number of ways to become better suited for infection and the environmental cues responsible for initiating these transitions are numerous. Hallmarks of an infectious form of _C. albicans_ include robust growth, filamentation, biofilm production and resistance to antifungal agents. The studies included herein will focus on these yeast characteristics to determine whether microgravity represents an environmental cue with the potential to alter virulence. Due to limited access and the expense of spaceflight opportunities, ground-based simulators, such as rotating wall vessels or random positioning machines, have been used to generate a'modeled microgravity' environment in order to predict the response of cells to spaceflight microgravity [28; 29; 30; 31; 32; 33]. High Aspect Ratio Vessels (HARV) are rotating-wall vessels that, by revolving about an axis perpendicular to the gravitational vector, create a state of functional weightlessness and minimal fluid shear within the chamber. Low-fluid shear may indeed be an important environmental signal for organisms cultivated in microgravity. Reduced convection and diminished bulk flow may resulted in an altered cell-associated microenvironment through depletion of nutritional components and accumulation of waste products [34].