The impact of clinical trials on patient care depends on the outcomes that they evaluate. In Dentistry, many trials use outcomes that are important to clinicians, but not to the patients. Thus, the aim of the present manuscript is to present an overview of the limitations, challenges, and proposals on the use of clinically relevant outcomes (CRO) in dental trials. Clinically relevant outcomes are variables that directly measure how the patient feels, functions, or survives. Some CROs, such as tooth loss, implant failure, and restorations failure require many years to occur and the number of events is low. The adoption of these variables as primary outcomes results in challenges for the researchers, such as use of large sample sizes and long follow-up periods. Surrogate outcomes, such as biomarkers, radiographic measurements and indexes, are frequently used to replace CROs. However, they present many limitations, since the effect of the treatment on a surrogate does not necessarily reflect a change in the clinical outcome. Some proposals for the adoption of CROs are presented, such as the development of core outcome sets within each dental specialties and the organization of multi-center clinical trials.