In most organisms, circadian rhythms are generated by a molecular clockwork involving so-called clock genes. These circadian clock genes participate in regulatory feedback loops, in which proteins regulate their own expression. The outcome is that ribonucleic acids (RNAs) and proteins produced from many of these genes oscillate with a circadian rhythm. Here, we describe the regulation of clock genes and proteins, as deduced from work in rodents. Furthermore, we summarize the work done on human clock genes and their expression in peripheral tissues. Importantly, the research reviewed here points to an implication of clock gene defects in circadian rhythm disorders, including the advanced and delayed sleep phase disorders. Moreover, circadian clock gene dysfunction is likely to be of importance in the development of cancer as well as various other diseases.