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<i>Weissella</i> is a genus earlier considered a member of the family <i>Leuconostocaceae,</i> which was reclassified into the family <i>Lactobacillaceae</i> in 1993. Recently, there have been studies emphasizing the probiotic and anti-inflammatory potential of various species of <i>Weissella</i>, of which <i>W. confusa</i> and <i>W. cibaria</i> are the most representative. Other species within this genus include: <i>W. paramesenteroides, W. viridescens, W. halotolerans, W. minor, W. kandleri, W. soli, W. ghanensis, W. hellenica, W. thailandensis, W. fabalis, W. cryptocerci, W. koreensis, W. beninensis, W. fabaria, W. oryzae, W. ceti, W. uvarum, W. bombi, W. sagaensis, W. kimchi, W. muntiaci, W. jogaejeotgali, W. coleopterorum, W. hanii, W. salipiscis,</i> and <i>W. diestrammenae. Weissella confusa, W. paramesenteroides, W. koreensis,</i> and <i>W. cibaria</i> are among the few species that have been isolated from human samples, although the identification of these and other species is possible using metagenomics, as we have shown for inflammatory bowel disease (IBD) and healthy controls. We were able to isolate <i>Weissella</i> in gut-associated bacteria (post 24 h food deprivation and laxatives). Other sources of isolation include fermented food, soil, and skin/gut/saliva of insects/animals. With the potential for hospital and industrial applications, there is a concern about possible infections. Herein, we present the current applications of <i>Weissella</i> on its antimicrobial and anti-inflammatory mechanistic effects, the predisposing factors (e.g., vancomycin) for pathogenicity in humans, and the antimicrobials used in patients. To address the medical concerns, we examined 28 case reports focused on <i>W. confusa</i> and found that 78.5% of infections were bacteremia (of which 7 were fatal; 1 for lack of treatment), 8 were associated with underlying malignancies, and 8 with gastrointestinal procedures/diseases of which 2 were Crohn’s disease patients. In cases of a successful resolution, commonly administered antibiotics included: cephalosporin, ampicillin, piperacillin-tazobactam, and daptomycin. Despite reports of <i>Weissella</i>-related infections, the evolving mechanistic findings suggest that <i>Weissella</i> are clinically treatable bacteria with emerging antimicrobial and probiotic benefits ranging from oral health, skin care, obesity, and inflammatory diseases to cancer.