In medicine, randomized controlled trials (RCTs) are considered the gold standard for evaluating the efficacy and safety of new treatment paradigms and therapeutic advancements in medicine.1 As medicine advances, there is increasingly available access to stored healthcare information that gives more insight into a wider array of the patient population, particularly in respective fields of oncology. With the growth in the availability of healthcare information through databases is often referred to as “real-world data” (RWD). RWD includes information on patient evaluation and management and may better represent patient populations in clinical practice, rather than the carefully selected patients that are typically enrolled in RCTs. Unfortunately, the low cost to access large quantities of data have led to a surge in the use of RWD to emulate RCTs. Readers, patients, or media outlets often misattribute the results of RWD-based comparative effectiveness research (CER) as causal rather than a potentially erroneous or indirect association. The aims of the article are to: (1) describe the role of RCTs and retrospective database analyses with RWD, and (2) elucidate the different attributes of available databases for RWD in oncology.