Randomized clinical trials (RCTs) are human studies carried out to compare different treatments or interventions, and their results are used to support clinical decision-making and improve patient care. Herein, the aim of this study was to review the selection process of study outcomes in periodontology. Primary outcomes should draw the main conclusions of the study, whereas secondary outcomes should only be used to help explain the main findings and generate future research hypothesis. Outcomes are classified as clinically relevant (CROs) or surrogate outcomes. CROs - the first option for primary outcome variables - should convey not only substantial health benefits, but also be deemed important by patients. In periodontology, tooth loss/retention and oral health-related quality of life (OHRQoL) are examples of CROs. While tooth loss has main limitations as a primary outcome, emerging evidence suggest that patient-reported outcome measures (PROMs) can accurately detect OHRQoL following periodontal therapy. When CROs cannot be assessed, validated surrogate outcomes can be used as proxies. Primary outcome variables should reflect a treatment endpoint at the patient level that can be easily used to inform decision-making in daily practice. These outcomes should allow the implementation of a treat-to-target concept in which the intervention can be clearly judged against a prespecified treatment target. Recently, the presence of at most 4 sites with periodontal probing depth ≥5 mm post-treatment was suggested as an effective endpoint for periodontal trials. In perspective, a combination of validated clinical parameters and PROMs will provide a more comprehensive assessment of periodontal treatments.