Piperaquine was developed under the Chinese National Malaria Elimination Programme in the 1960s and was adopted throughout China as a replacement for the structurally similar antimalarial drug chloroquine.

[1] Like chloroquine, piperaquine is thought to function by accumulating in the parasite digestive vacuole and interfering with the detoxification of heme into hemozoin.

The epicenter of piperaquine resistance appears to be western Cambodia where in 2014 over 40% of dihydroartemisinin-piperaquine treatments failed to eliminate parasites from the patient's blood.

[5] Piperaquine was discovered in the 1960s by two separate groups working independently of one another: the Shanghai Pharmaceutical Industry Research Institute in China and the Rhone Poulenc in France.

[5] In the 1970s and 1980s piperaquine became the primary antimalarial drug of the Chinese National Malaria Control Programme due to increased parasite resistance to chloroquine.