Medicinal plants are a prominent source of secondary metabolites and bioactive innovative molecules with interesting and remarkable biological activities. The Sinai Peninsula is considered an exceptional reservoir of many indigenous medicinal plants that have been used for treatment of many ailments; Pulicaria is a promising medicinal genus and one of the widest spread desert plants growing wild in Egypt. Some plants within the genus are used as traditional herbal medicines. Pulicaria is a well-known natural source of several bioactive compounds and used in traditional medicine in the many countries. Most importantly, previous studies of Pulicaria species allowed the isolation of various compounds such as flavonoids and terpenes. Our review tends to support the therapeutic value of this genus. Many recent studies suggested that most of the reported biological activities of Pulicaria are due to its high content of polyphenols, particularly flavonoids. This review highlights the phytochemical constituents of this important and valuable genus as well as its different reported biological activities.