Aertsen's chief historical significance lies in his contribution to the development of small Netherlandish genre subjects, (popularized by the Bruegel workshop) into life-size, monumental paintings. His scenes of peasants in everyday domestic settings give weight to foreground detail, which is usually tilted toward the spectator. The figures are also close to the picture plane in half- or three-quarter-length, as in the Pancake Bakery of 1560 (Boymans-van Beuningen Museum, Rotterdam). In his rather humorless treatment of the figures, Aertsen rejects the moralizing or ironic comment found in Bruegel. His style is more sculptural, and closer to the Romanist school of Flemish painting. Sometimes an ostensibly genre subject provides the foreground for a religious scene, and takes visual precedence over it. For example, in the Butcher's Shop (Royal Collection of Uppsala University) the carefully arranged meat and cooking utensils of the foreground frame a scene of the Flight into Egypt seen through an opening on to the landscape.

Aertsen's genre subjects anticipate similar works by several late-16th-century Italian artists, notably Annibale Carracci. Technically, his vigorous, broad brushwork places him in the Flemish tradition that was to produce such artists as Rubens and Jordaens in the 17th century.