Enterotoxigenic Clostridium perfringens has been recognized as a ubiquitous human pathogen owing to, at least in part, three important characteristics. First, this bacterium undergoes asymmetric cell division or sporulation under nutritionally deprived conditions. Second, during sporulation growth it produces C. perfringens enterotoxin, an important virulence factor for food poisoning and nonfood-borne gastrointestinal diseases in humans. Third, at the final stage of sporulation, sporulating cells lyse to release mature dormant spores, which are resistant to high heat and can survive in the environment for long periods of time. Here, we present an overview of what is currently known about the mechanisms of sporulation, sporulation-regulated C. perfringens enterotoxin synthesis and spore heat resistance and we discuss their impact on the pathogenesis of C. perfringens.