Scaling and root planing is considered the gold standard treatment for periodontal diseases and leads to major clinical benefits, including reduction in bleeding on probing and probing depth, and gain in clinical attachment. However, scaling and root planing is not effective for all subjects, and may not prevent future disease progression in cases of patients with advanced/very advanced disease or with low levels of plaque and calculus. Thus, other forms of therapies, such as systemic antibiotics, host-modulators and probiotics have been suggested as adjuncts to scaling and root planing in order to potentiate its effects. Despite the fact that several Randomized Clinical Trials evaluating the benefits of these adjunctive treatments have been published in the past decade, the interpretation of these data is not a simple task, in part due to the great heterogeneity in the studies designs and to the divergence among the clinical outcome variables of different studies. This presentation endeavors to present and discuss the current literature on this topic in an attempt to determine the weight of evidence for the use of these adjunctive therapies in the periodontal treatment. The ultimate goal is to provide clinicians with guidance to make decisions in daily clinical practice.