Circadian timing from the suprachiasmatic nucleus (SCN) is a critical component of sleep regulation. Animal lesion and genetic studies have indicated an essential interaction between the circadian signals and the homeostatic processes that regulate sleep. Here we summarize the biological functions of prokineticins, a pair of newly discovered regulatory proteins, with focus on the circadian function of prokineticin 2 (PK2) and its potential role in sleep-wake regulation. PK2 has been shown as a candidate SCN output molecule that regulates circadian locomotor behavior. The PK2 molecular rhythm in the SCN is predominantly controlled by the circadian transcriptional/translational loops, but also regulated directly by light. The receptor for PK2 is expressed in the primary SCN output targets that regulate circadian behavior including sleep-wake. The depolarizing effect of PK2 on neurons that express PK2 receptor may represent a possible mechanism for the regulatory role of PK2 in circadian rhythms.