Probiotics are live microorganisms. When they were administered in adequate amounts, they could have beneficial effects on the host. They are generally applied in food fermentation, industrial lactic acid production and medical care. With the appearance of commercial probiotics, more concerns were raised on the safety of probiotics. At present, there were four aspects of safety concerns on probiotics: pathogenicity and infectivity; deleterious metabolic activities; excessive immune response and potential gene transfer. Conventional toxicology and safety evaluation has limited value in the safety assessment of probiotics used in marketing food and drugs nowadays. Instead, multidisciplinary approaches are necessary for the systematical safety evaluation of probiotic strains. It may involve genomics, metabolismics, proteomics, among others. The toxigenic metabolic activity should be considered especially. We reviewed recent developments and research methods on the safety of probiotics. Safety evaluation of the lactic acid bacteria for human consumption must be assessed by proposing criteria standards, guidelines and regulations, for better applications for consumers.