Probiotics are often referred to as microorganisms (bacteria or yeasts) that generally provide health benefits. There is great interest in probiotics for various medical reasons and millions of people around the world consume probiotic microorganisms daily with the perception that it is beneficial for health. Members of the genus Lactococcus and Lactobacillus, Streptococcus, Enterococcus strains, and some other LAB strains are generally accepted as safe (GRAS) status, although they contain some opportunistic pathogens. In addition, some of the spore forming bacteria have been researched and used as probiotics. However, nowadays theoretical concerns and side effects are discussed with regard to the safety of probiotics. Systemic infections, the risk of harmful metabolic activities, risk of adjuvant side effects, immunomodulation and gene transfer risk are among the theoretical concerns discussed. The most common side effects of probiotic microorganisms include gastrointestinal disorders such as nausea, diarrhea, bloating, abdominal pain and dyspepsia. Other side effects include respiratory tract infections, abscess, allergic reactions and severe medical conditions such as sepsis, endocarditis and fungemia. The safety of probiotics is related to the potential vulnerability of the consumer or the patient, the dose of use, duration of consumption and the frequency of consumption. The significance of negative probiotic effects will be better understood by understanding of the probiotic interaction mechanisms with host and colonizing microbes. In this chapter, the evaluation of the risk associated with the consumption of probiotic products has been discussed, based on epidemiological data and infected cases.