The long history of safety has contributed to the acceptance of probiotics as a safe food adjunct. Consequently, many probiotic products and their applications have been granted GRAS (generally regarded as safe) status. However, this classification has been frequently generalized for all probiotic strains regardless of their application. Cases of probiotics from the genera Lactobacillus, Leuconostoc, Pediococcus, Enterococcus, and Bifidobacterium have been isolated from infection sites, leading to the postulation that these probiotics can translocate. Probiotic translocation is difficult to induce in healthy humans, and even if it does occur, detrimental effects are rare. Despite this, various reports have documented health-damaging effects of probiotic translocation in immunocompromised patients. Due to probiotics' high degree of safety and their morphological confusion with other pathogenic bacteria, they are often overlooked as contaminants and are least suspected as pathogens. However, the antibiotic resistance of some strains has increased the complexity of their eradication. Probiotic translocation and infection deserve further investigation and should become a facet of safety assessment so the negative effects of probiotics do not outweigh the benefits.