The first attempts at developing an odor-based form of crowd control began in Israel in 2004 by Rafael. The IDF reconsidered at the time a change in its open fire procedures, and adopting other crowd dispersal methods after an Israeli demonstrator, Gil Na'amati (21), was shot during a protest over the separation barrier, near the West Bank village of Mas-ha in late 2003. It reportedly does not wash off easily and may linger on clothes for up to five years. The development of Skunk followed numerous accusations against Israeli forces that they often employ disproportionate force in clashes with Palestinian protestors (e.g. using rubber bullets or tear gas), which has led them to seek new, non-lethal but effective methods of crowd control.
Skunk was first reported to be used for crowd control in August 2008 in the Palestinian village of Nilin where daily protests had been taking place in response to the construction of a security barrier. Spraying the liquid has developed into one of the preferred measures adopted by the IDF to meet the challenge of civil disobedience and demonstrations by Palestinians.  The tactic was devised to tamp down organized civilian protests in the West Bank. It has been used regularly against the villagers of Bilin, Ni'lin, Kafr Qaddum, and Nabi Salih, where weekly protests against the occupation are practiced.
In Hebron it was used on the 26 February 2012 to disperse a crowd of an estimated 1,000 people which clashed with Israeli soldiers during a protest described as commemorating the anniversary of the Cave of the Patriarchs Massacre or as pressing for the reopening of the zone of Shuhada Street.  A funeral procession waiting for the riots to be dispersed were also doused with the liquid.  It has been used during clashes with "Palestinian protesters calling for the release of Palestinian hunger striker Mohammad Allan near Barzilai Medical Center" in the Israeli city of Ashkelon.
In 2017, Israeli forces began using Skunk against ultra-Orthodox Jewish protesters.
In January 2024, students at a pro-Palestine demonstration at Columbia University were allegedly attacked with Skunk by individuals disguised as fellow protesters. One victim, who claimed that Palestinian friends recognized the odor as Skunk, described it as having the smell of "poop mixed with decaying animal." Victims of the attack reported difficulty removing the odor from their clothes and other possessions, and that the effects of the spray including its odor, skin irritation, nausea, and dizziness continue days after the attack despite efforts to remove it. The incident is currently being investigated by the New York City Police Department as a potential hate crime.