The number of clinical studies in the field of orthopedics is overwhelmingly large and continually growing. There are several major types of research questions that researchers can answer. These are typically classified into therapy, prognosis, diagnosis, and economic questions. This chapter focuses on those studies addressing therapy, as this is generally the most common type of study in the orthopedic surgical literature. Randomized clinical trials (RCTs) can demonstrate the superiority of a new treatment over an existing standard treatment or a placebo, or they can demonstrate that a new treatment is noninferior to an established treatment. Well‐designed RCTs can provide good measures of the effect of treatments administered under ideal conditions. Observational studies inform clinicians about disease etiology, natural history, prognostic factors, and sometimes treatment effectiveness. In most evidence hierarchies, well‐designed systematic reviews and meta‐analyses of level I evidence are at top of the pyramid, and expert opinion and anecdotal experience are at the bottom.