This chapter reviews the approaches that have been used to identify genomic variation that may shape circadian entrainment and point new directions of research. It addresses some issues concerning study designs that may increase the efficiency of finding genetic components of the circadian clock in human. If the inter-individual differences in human time-of-day preference or in chronotype are extreme, they can manifest themselves as familial syndromes. The application of ethnicity markers is meanwhile a routine strategy in genome-wide association (GWA) studies. The GWA strategy is more reliable than a candidate gene approach. Human entrainment to different photoperiods may involve substantial plasticity in individual circadian period and phase of entrainment. High-throughput analyses are applied in circadian rhythms research. The authors have recently applied high-throughput genomics to identify alleles associated with phase of entrainment in extreme chronotypes.