The use of sulfur dioxide (SO2) as wine additive is able to ensure both antioxidant protection and microbiological stability. In spite of these undeniable advantages, in the last two decades the presence of SO2 in wine has raised concerns about potential adverse clinical effects in sensitive individuals. The winemaking industry has followed the general trend towards the reduction of SO2 concentrations in food, by expressing at the same time the need for alternative control methods allowing reduction or even elimination of SO2. In the light of this, research has been strongly oriented toward the study of alternatives to the use of SO2 in wine. Most of the studies have focused on methods able to replace the antimicrobial activity of SO2. This review article gives a comprehensive overview of the current state‐of‐the‐art about the chemical additives and the innovative physical techniques that have been proposed for this purpose. After a focus on the chemistry and properties of SO2 in wine, as well as on wine spoilage and on the conventional methods used for the microbiological stabilization of wine, recent advances on alternative methods proposed to replace the antimicrobial activity of SO2 in winemaking are presented and discussed. Even though many of the alternatives to SO2 showed good efficacy, nowadays no other physical technique or additive can deliver the efficacy and broad spectrum of action as SO2 (both antioxidant and antimicrobial), therefore the alternative methods should be considered a complement to SO2 in low‐sulfite winemaking, rather than being seen as its substitutes.