Clostridium difficile causes ~500,000 infections each year and is the leading cause of antibiotic-associated diarrhea and gastroenteritis-associated death in the United States. We study how C. difficile forms infectious spores and how these spores germinate upon sensing specific bile salts in the mammalian gut. Spore formation and germination are essential for C. difficile to transmit disease, and analyses of these processes have revealed major differences relative to previously studied spore formers. We use a multi-disciplinary approach to identify regulators of these processes and elucidate their mechanisms of action. A better understanding of the basic biology of C. difficile sporulation and spore germination should facilitate the development of spore-specific therapies that can prevent C. difficile disease transmission.