Tea is the most popular functional beverage in the world and has been gaining more and more attention for its health beneficial properties. Among common teas, black tea is consumed more than green tea and oolong tea worldwide. Numerous studies have shown the biological activities of black tea and its polyphenols that include anti-oxidant, anti-tumor, anti-inflammation and metabolic regulation. Tea polyphenols such as theaflavins and catechins are considered to be multifunctional compounds that could be effective in the prevention or treatment of various cancers, cardiovascular disease, chronic inflammation, obesity, metabolic syndrome, and neurodegenerative diseases. In this review, we summarized the up-to-date research and underlying molecular mechanisms of black tea and its polyphenols.