The term big data has been popularized over the past decade and is often used to refer to data sets that are too large or complex to be analyzed by traditional means. Although the term has been utilized for some time in business and engineering, the concept of big data is relatively new to medicine. The reception from the medical community has been mixed; however, the widespread utilization of electronic health records in the United States, the creation of large clinical data sets and national registries that capture information on numerous vectors affecting healthcare delivery and patient outcomes, and the sequencing of the human genome are all opportunities to leverage big data. This review was inspired by a lively panel discussion on big data that took place at the 75th Central Surgical Association Annual Meeting. The authors’ aim was to describe big data, the methodologies used to analyze big data, and their practical clinical application.