Benzofuran is a fundamental structural unit in a variety of biologically active natural products, and its derivatives display various biological properties. Some benzofuran derivatives possess unique anti-tubercular and anti-bacterial action mechanism, and exhibit excellent in vitro and in vivo activities against both drug-sensitive and drug-resistant pathogens. Moreover, several benzofuran derivatives have already used in clinics for the treatment of various diseases. Thus, benzofuran is a useful pharmacophore to develop new anti-tubercular and anti-bacterial drugs. This review covers the recent advances of benzofuran derivatives as potential anti-tubercular and anti-bacterial agents, and the structure-activity relationship is also discussed to pave the way for the further rational development of this kind of derivatives.