There are many variations to the classical randomized controlled trial. These variations are utilized when, for a variety of reasons, the classical randomized controlled trial would be impossible, inappropriate, or impractical. Some of the variations are described in this chapter and include: equivalence and noninferiority trials; crossover trials; N of 1 trials, case-crossover trials, and externally controlled trials. Large simple trials, and prospective randomized, open-label, blinded endpoint trials are discussed in another chapter. © Springer Science + Business Media B.V. 2008.