Probiotics defined as live microorganisms, which when administered in adequate amounts, confer a health benefit on the host is now more relevant than ever before, with few concerns raised on toxicity potential. This review examined the safe use of probiotics in chronically ill patients and cases of adverse effects. Safety assessment for the selection of probiotics and toxicological related animal/human studies were evaluated based on Pubmed search for allied articles. There were conflicting reports on the safety use of probiotics in immunocompromized patients, with few isolated cases of bacteraemia in patients with underlying co-morbidities. Probiotic strains are less likely to participate in the pathogenesis of infections in healthy individuals. This is based on the fact that each year, >20 billion doses of probiotics are used by healthy people and by those diagnosed with a range of medical conditions. Conventional toxicology and safety evaluation employed for pharmaceutical products may be of limited value in assessing the safety of probiotics. If probiotic toxicology is to be developed, then a threshold defined as a dose at or below which a response is not seen in an experimental setting will have to be evaluated. Establishing proof of absence of an effect at such a dose in absolute terms is scientifically and practically demanding. There is no evidence or documentation that lactic acid bacteria used as probiotics do synthesize any toxins detrimental to humans. However, as probiotics is safe in healthy people, immuno-compromised individuals should consult their health care providers before using probiotics.