Substance P (SP) is a neuropeptide that is a neurotransmitter and a neuromodulator in the central and peripheral nervous system. SP is known to have regulatory effects on nervous or non nervous cells, including immune cells. SP is involved in the physiopathology of local inflammation, including inflammatory dermatoses. The purpose of this review is to relate the localization of SP and its receptors to illustrate the immunomodulatory functions of SP through its effects on various immune cells and to focus on the localization of SP in human skin and on its effects on cutaneous cells. The probable implication of SP in inflammatory dermatoses will be discussed.