Sourdough remained the usual form of leavening down into the European Middle Ages until being replaced by barm from the beer brewing process, and after 1871 by purpose-cultured yeast.

Bread made from 100% rye flour, popular in the northern half of Europe, is usually leavened with sourdough. Baker's yeast is not useful as a leavening agent for rye bread, as rye does not contain enough gluten. The structure of rye bread is based primarily on the starch in the flour as well as other carbohydrates known as pentosans; however, rye amylase is active at substantially higher temperatures than wheat amylase, causing the structure of the bread to disintegrate as the starches are broken down during baking. The lowered pH of a sourdough starter, therefore, inactivates the amylases when heat cannot, allowing the carbohydrates in the bread to gel and set properly. In the southern part of Europe, where panettone is still made with sourdough as leavening, sourdough has become less common in the 20th century; it has been replaced by the faster-growing baker's yeast, sometimes supplemented with longer fermentation rests to allow for some bacterial activity to build flavor. Sourdough fermentation has re-emerged as a major fermentation process in bread production in the past ten years although it is commonly used in conjunction with baker's yeast as leavening agent.