The International Journal of Molecular Sciences Special Issue "Serotonin in health and diseases" covers several aspects of the multiple and still mysterious functions of serotonin (5-hydroxytryptamine; 5-HT). 5-HT is neurotransmitter acting in the central nervous system (CNS), blood factor, and neurohormone controlling the function of several peripheral organs. Beyond its widespread implication in physiology, the 5-HT system is involved in numerous diseases of the CNS (e.g., depression, anxiety, schizophrenia, obsessive-compulsive disorders, addiction, Parkinson's disease) and peripheral organs (e.g., gastrointestinal disorders, cardiac arrhythmia, hypertension). The Special Issue includes 14 articles dealing with molecular and cellular effects of 5-HT in periphery and CNS, from functional aspects in lower animals to clinical practices. Beyond physiology, the Special Issue also covers the influence of 5-HT and its receptors in the mechanism of action of psychoactive molecules including antipsychotics, antidepressants, and drug of abuse. The recent progress made on the function and dysfunction of the 5-HT system will certainly increase the understanding of the widespread role of 5-HT ultimately leading to better apprehend its targeting in human diseases.