Introduction As a traditional Chinese medicinal herb and food supplement, Lycium barbarum berries (also named wolfberry, Fructus lycii, Gouqizi, and Goji berries) have been used in the People’s Republic of China and other Asian countries for more than 2,000 years.1,2 The berries have become increasingly popular in Western countries as an anti-aging and antioxidant product.3 L. barbarum fruits (LBFs; Figure 1A), which are red-colored and sweet in taste, are mainly found in Ningxia Province. People’s Republic of China. These berries are eaten raw and drunk as a juice, wine, or tea. These berries also be processed to tinctures, powders, and tablets. Traditional Chinese medicine considers L. barbarum berries to have the ability to maintain the function of eyes and strengthen the activity of liver, kidneys, and lungs via boosting and balancing “Yin” and “Yang” in the body.1,2 LBFs contain abundant polysaccharides (LBPs, comprising 5%–8% of the dried fruits), scopoletin (6-methoxy-7-hydroxycoumarin, also named chrysatropic acid, ecopoletin, gelseminic acid, and scopoletol), the glucosylated precursor, and stable vitamin C analog 2-O-β-D-glucopyranosyl-L-ascorbic acid, carotenoids (zeaxanthin and β-carotene), betaine, cerebroside, β-sitosterol, flavonoids, amino acids, minerals, and vitamins (in particular, riboflavin, thiamin, and ascorbic acid).4 The predominant carotenoid is zeaxanthin, which exists mainly as dipalmitate (also called physalien or physalin). The content of vitamin C (up to 42 mg/100 g) in wolfberry is comparable to that of fresh lemon fruits. As to the seeds, they contain zeaxanthin (83%), β-cryptoxanthin (7%), β-carotene (0.9%), and mutatoxanthin (1.4%), as well as some minor carotenoids.1 In fact, increasing lines of experimental studies have revealed that L. barbarum berries have a wide array of pharmacological activities, which is thought to be mainly due to its high LBPs content. Water-soluble LBPs are obtained using an extraction process that removes the lipid soluble components such as zeaxanthin and other carotenoids with alcohol. LBPs are estimated to comprise 5%–8% of LBFs and have a molecular weight ranging from 24 kDa to 241 kDa. LBPs consist of a complex mixture of highly branched and only partly characterized polysaccharides and proteoglycans (Figure 1B). The glycosidic part accounts, in most cases, for about 90%–95% of the mass and consists of arabinose, glucose, galactose, mannose, rhamnose, xylose, and galacturonic acid.5,6 LBPs are considered the most important functional constituents in LBFs. Different fractions of LBPs have different activities and the galacturonic acid content is an imperative factor for activities of LBP. The bioactivities of polysaccharides are often in reverse proportion with their molecular weights. Increasing lines of evidence from both preclinical and clinical studies support the medicinal, therapeutic, and health-promoting effects of LBPs. Herein, we update our knowledge on the main pharmacological activities and possible underlying mechanisms of LBPs with a focus on the molecular targets and signaling pathways involved. For more information on the phytochemistry, pharmacology, and biology of Goji berries and LBPs, please read recent reviews.1,3,7–9