Understanding how sleep-wake schedules are biologically determined via cellular circadian rhythmicity may reveal potential treatments for circadian rhythm sleep disorders (CRSDs). Familial advanced sleep phase (FASP) is the first human Mendelian circadian rhythm trait to be identified. FASP is expected to exhibit an autosomal dominant mode of inheritance, and phenotyping and obtaining DNA from related individuals aids genetic analysis. As self-reported data are subjective, physiological circadian rhythm measurements are crucial for supporting self-reported data. With the advent of high-throughput genotyping methods and growing knowledge of circadian components, novel genetic variants can now be identified through both recombination mapping and candidate approaches. Animal models remain essential for proving genetic causation, especially for evaluating behavioral traits such as sleep-wake timing. This chapter discusses a practical framework for investigating the human genetic basis of sleep and other complex behaviors.