Arsenic is known as a toxic metalloid, which mainly exists in inorganic forms such as arsenite and arsenate in the natural environment. A number of microorganisms have evolved different resistant mechanisms for arsenic detoxification to cope with the widespread distribution of the poisonous arsenic. Four distinct microbial arsenic-resistant mechanisms have been described including As(III) oxidation, cytoplasmic As(V) reduction, respiratory As(V) reduction, and As(III) methylation. These mechanisms confer arsenic resistance in microorganisms that play important roles in the transformation and geological cycle of arsenic. This review mainly focuses on the researches on these molecular mechanisms and potential application for environmental arsenic bioremediation using microorganisms.