Annona squamosa L. (Annonaceae) is a fruit tree with a long history of traditional uses. A. squamosa is an evergreen plant mainly located in tropical and subtropical regions. Srikayas, the fruits of A. squamosa, are extensively used to prepare candies, ice creams and beverages. A wide range of ethno-medicinal uses has been related to different portions of A. squamosa, such as tonic, apophlegmatisant, cool medicine, abortient and heart sedative. Numerous research projects on A. squamosa have found that it has anticancer, anti-oxidant, antidiabetic, antihypertensive, hepatoprotective, antiparasitic, antimalarial, insecticidal, microbicidel and molluscicidal activities. Phytochemistry investigations on A. squamosa have considered annonaceous acetogenins (ACGs), diterpenes (DITs), alkaloids (ALKs) and cyclopeptides (CPs) as the main constituents. Until 2016, 33 DITs, 19 ALKs, 88 ACGs and 13 CPs from this species were reported. On the basis of the multiple researches on A. squamosa, this review strives to integrate available information on its phytochemicals, folklore uses and bioactivities, hoping to promote a better understanding of its medicinal values.