The concept of hypnogenic factor(s) which could increase during sleep deprivation was initiated by Piéron in 1913. However this idea was not accepted. It is difficult indeed to differentiate a true sleep inducing factor from the numerous exogeneous or endogeneous factors which may facilitate sleep onset, slow wave sleep (SWS) and/or paradoxical sleep (PS). At the present time there is no true sleep inducing factor for which it has been proven that its inactivation would led to long lasting selective insomnia. A review of the effect of central peptides upon the sleep waking cycle of rats does not permit to isolate any true "sleep" peptide. Only vaso-intestinal peptide (VIP) has some true hypnogenic effect since its injection is able to restore sleep in insomniac PCPA pretreated rats. The serotonergic system of the raphe was considered first as a true hypnogenic system since its inactivation by lesion or inhibition of 5HT biosynthesis with PCPA led to a total insomnia which could be reversed into physiological sleep by a secondary injection of 5HTP (the direct precursor of 5HT). This hypothesis has been rejected recently. Indeed, it has been shown that the activity of 5HT neurons was higher during waking than during sleep. Moreover the release of 5HT and 5HIAA (as measured with voltametric method) is also higher during waking. The following hypothesis may solve these contradictions: when 5HT neurons are active during waking, they initiate through neurohormonal mechanisms the biosynthesis of sleep factor(s) which are stored until they trigger sleep. Thus the amount of waking may be correlated with subsequent sleep. Recent experiments favor the hypothesis of the 5HT directed biosynthesis of PS factor which may trigger PS even in PCPA pretreated cats which are depleted of 5HT. On the one hand, PCPA injection during PS instrumental deprivation is followed by a subsequent PS rebound despite 5HT depletion. On the other hand, transfer of CSF from a normal sleep deprived donor cat induces PS in a PCPA pretreated insomniac recipient cat.