Evidence-based medicine is defined as “the conscientious, explicit and judicious use of current best evidence about the care of individual patients integrated with clinical expertise and patient values to optimize outcomes and quality of life”. In the hierarchy of study designs used in clinical research, randomized controlled trials (RCT), prospective controlled trials (CT) and meta-analyses (MA) or systematic reviews (SRs) of RCTs are considered to provide the highest level of evidence. Conversely, uncontrolled studies like case series and case reports, as well as retrospective studies, due to the features of the study design and many methodological aspects that may somehow affect the outcome reliability, are considered to have a higher risk of bias as compared to RCTs. The latter are specifically designed to minimize the experimental bias in any step of the study procedures, so as to provide the most reliable possible outcomes. Clinical guidelines based on SRs of RCTs represent the most valuable process to formulate recommendations which should be followed in the decision-making procedure. Only in the absence of trustful evidence can recommendations be based on expert opinion. Since the volume of published information is steadily increasing, it is extremely important to assess the level of evidence of the publications in order to discern which information can be relied upon to formulate an evidence-based treatment plan and provide patients with the most accurate, up-to-date and trustworthy information. The purpose of this chapter is to provide the basis of the evidence-based dentistry in order to facilitate clinicians in their daily decision-making process.