Clinical trials are an especially powerful study design that often guides health care policy and clinical practice. Indeed, well-designed and rigorously conducted trials can establish the etiologic relevance of modifiable risk factors and the benefits (and risks) of candidate therapies. Contemporary schema that classify evidence place results from randomized trials at the pinnacle of evidence. The primary objective of this article is to provide an overview of the design, conduct, and interpretation of trials with an emphasis on aspects that are relevant to nephrology.