Saccharomyces cerevisiae (brewer's or baker's yeast) is a common colonizer of human mucosal surfaces, but its role as a clinically important pathogen has been unclear. We report three cases of life-threatening invasive infection with S. cerevisiae resulting in pneumonia, liver abscess and sepsis, and disseminated infection with cardiac tamponade, respectively. A review of the English-language literature reveals 14 other cases of saccharomyces infection in humans. Severe immunosuppression, prolonged hospitalization, prior antibiotic therapy, and/or prosthetic cardiac valves are the settings where saccharomyces infection has been observed. Because Saccharomyces can be a common saprophytic contaminant, biopsy and pathologic confirmation of infection are often necessary for a definitive diagnosis. Amphotericin B is the treatment of choice for serious infections with this organism.