Orthodontics is not only an art but also a science, and the key to practicing it likewise lies with implementing evidence-based orthodontics (EBO). Systematic reviews (SRs) and Meta-analyses (MAs) are considered to be the "gold standard" or highest level of evidence in EBO. The limitations of traditional, narrative reviews have led to the increased popularity of SRs due to their objective and transparent methodology, which makes the evidence generated by them more reliable and unbiased. With SRs and MAs becoming the mainstay of Orthodontic research and EBO, it is imperative to be in the know of the technicalities of these tools of research synthesis. The present paper provides an overview of the SR methodology and describes in detail the key steps in conducting SRs or MAs viz., formulating the review question, defining the criteria for inclusion of studies, identifying all relevant studies by a meticulous search process, including studies which meet pre-defined criteria, assessing quality of included studies and finally analysing and interpreting the collective findings from included individual studies. The paper can thus be used as a guide for the whats, whens, whys and hows of carrying out a systematic review and meta-analysis, and generate the highest quality of evidence available for delivering the best patient care.