The concept of multi-commutation in flow analysis is revisited, and emphasis is given to recent methodological and applicative achievements. Multi-commutation is compatible with different flow patterns (unsegmented, segmented, pulsed, tandem) and amenable to concentration-oriented feedback mechanisms. Its exploitation has led to significant attainments mainly in relation to versatility of the flow system. Characteristics and potentialities of the multi-commuted flow systems are discussed, and guidelines for assisting methodological implementation are given. The number of applications has experienced remarkable increase during last years; therefore, the applicative part of this review is focused on the recent noteworthy applications, mainly in relation to environmental, agronomical, pharmaceutical, biological, food and industrial samples.