Lactic acid bacteria (LAB) and Bifidobacteria are taxonomically distinct groups of bacteria with proven biotechnological properties such as anti-cancer, immune-stimulating, anti-microbial, maintenance of normal flora balance, probiotics, anti-inflammatory, vaccine carriers, among others. However, studies have implicated some of them, including the ones under the European Food Safety Authority (EFSA) qualified presumption of safety in fatal human and veterinary diseases. We performed online database searches of publications on Google, Google Scholar and PubMed using the criteria, “lactic acid bacteria, bifidobacteria as causative agents of human, animal diseases”. Data generated showed LAB across genera and Bifidobacteria either primarily or opportunistically involved in diseases of both immuno-competent and immuno-depressed humans and animals. The members of lactobacilli such as Lactobacillus fermentum, Lactobacillus paracasei, Lactobacillus oris, Lactobacillus gasseri and Leuconostoc mesenteroides, were mainly implicated in nosocomial infections, endophthalmitis, neonatal meningitis, and bacteraemia while Lactobacillus delbrueckii and Bifidobacteria, specifically, Bifidobacterium longum, Bifidobacterium breve, and Bifidobacterium animalis were implicated in urinary tract infections (UTIs), necrotizing pancreatitis, fatal pulmonary infections, sepsis, and epidural abscess. The animal diseases, neonatal sepsis in foal, was caused by Weissella confusa while the fish pathogen, Lactococcus garvieae caused various zoonotic cases such as acute acalculous cholecystitis in human. In conclusion, this review showed the up-to-date reports on LAB and Bifidobacteria implicated in serious humans and animal diseases.