Introduction: This review aimed to provide a critical appraisal of alternative antimicrobial strategies in lieu of traditional triple antibiotic paste (TAP). Methods: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The literature search was performed in 8 databases (PubMed/Medline, Embase, LILACS, Web of Science, Scopus, BVS, SciELO, and the Cochrane Library), selecting clinical, in vitro, in vivo, and in situ studies that evaluated antimicrobial alternatives to TAP in regenerative endodontics. Studies lacking an experimental TAP group were excluded. Results: A total of 1705 potentially relevant records were initially identified. From the 38 studies retrieved for fulltext reading, 16 fulfilled all selection criteria and were included in the qualitative analysis. According to the study design, 11 studies were solely in vitro, 1 study was both in vitro and in vivo (animal model), 2 studies were solely animal experiments, and 2 studies were clinical trials. The alternative antimicrobial agents to TAP consisted of modified TAP formulations (eg, a combination of TAP with chitosan); TAP-eluting nanofibers; propolis; chlorhexidine (CHX) gels/solutions; double antibiotic pastes composed of distinct combinations of antibiotics; Ca(OH) 2-based formulations; and sodium hypochlorite. Overall, most of the alternative agents performed similarly to TAP, although some strategies (eg, Ca(OH) 2-and CHX-based formulations) seemed to present dubious importance in the control of infection. Conclusions: TAP still remains an excellent option in terms of the complete elimination of microorganisms. This review points to the use of electrospun fibers as a drug delivery system to offer a controlled release of the antimicrobial agent, as well as the use of natural compounds, deserving future investigation. (J Endod 2020;46:S115-S127.) KEY WORDS Antimicrobial agents; natural compounds; regenerative endodontics; scoping review Regeneration of pulp tissue holds the promise of prolonged use of the natural dentition through predictable maintenance of dental root structure. Although the field of endodontics has been aware that healthy pulp tissue exists within infected/inflamed pulp, resective therapy has been the standard of care 1. However, in cases where pulp necrosis occurs in permanent teeth with open apex, the most commonly used treatment is apexification 2. This technique is based on the use of calcium hydroxide [Ca(OH) 2 ] or mineral trioxide aggregate (MTA) to induce hard tissue apical barrier formation 3 and presents success rates that vary from 26% to 100%. Nonetheless, the major intrinsic disadvantage of this therapy is that these teeth have thin dentin walls, open apex, and, consequently, an increased risk of cervical fracture 4,5. From a biological viewpoint, Ca(OH) 2 was demonstrated to induce cell proliferation as well as stem cell survival, although only under the use of low concentrations of that compound 6,7. According to Khoshkhounejad et al 8 , cell viability was...