This review examines current knowledge regarding the safety of probiotic bacteria in man. Tighter and more comprehensive standards and regulations will be developed as probiotic therapy moves from a limited number of products used in the food industry, into more defined therapeutic categories and more complex organisms. A new framework considering probiotics as nonspecific promoters of mucosal immunity, defines probiotic characteristics and the clinical circumstances in which it is used. For example, those with immune deficiency taking a high dose of viable bacteria may have an increased risk. A wider range of bacteria is now being used, sometimes in territories other than the gut mucosa. The question of competition with multiple isolates must be addressed, as does the use of nonselected faecal isolates. Transfer of antibiotic resistance with probiotics acting as a 'shuttle' needs clarification. These issues are addressed and reviewed as probiotics evolve into a new therapeutic arena.