Breastfeeding is considered the gold standard for infants' nutrition and provides unique benefits for infants' health. Great research interest has been raised about the use of bioactive components in neonatal medicine, both as standalone products and as addition to infant formula, in the attempt to reproduce human milk beneficial effects. Thus, the aim of this narrative review is to summarize most recent evidence on biotics' use in the neonatal period, with a focus on infant formula (IF) supplemented with probiotics, prebiotics, synbiotics and postbiotics. Growing data indicate overall positive effects of biotic supplemented formula on microbiome composition and metabolic activity. Furthermore, some benefits are also emerging from randomized controlled trials evaluating the clinical impact these enriched formulas may have on the health of formula fed infants. However, clear evidence still lacks and none of this supplemented IF has demonstrated conclusive superiority. To date, whereas no routine recommendations can be done, biotics supplemented IF have generally proven to be well-tolerated and safe in ensuring infants' normal growth, paving the way for future IF alternatives for those infants who are not able to be (fully) breastfed. More RCTs, with adequate design and statistical power, are still needed to better clarify, if present, which benefits the supplementation of IF may confer to infants' short and long-term outcomes.