Between 1639 and 1658, the house was occupied by the Dutch painter Rembrandt van Rijn, who also had his studio and art dealership there.

At the beginning of the 20th century, the building was in poor condition, and on the occasion of the Rembrandt Year in 1906, it was purchased in 1907 by the municipality of Amsterdam, which donated it to the Rembrandthuis foundation.

Since Rembrandt used the house for his own collection of works by others, and as a gallery for his career as an art dealer, this is believed to reflect well its appearance while he lived there.

The new acquisition is the painting Shepherdess in a Landscape from c. 1641, made by Ferdinand Bol, one of Rembrandt's most famous pupils.

In 2022, the museum purchased four contemporary works of art by Natasja Kensmil and Milan Gies.

The museum also owns contemporary art by (amongst others) Marlene Dumas, Reinder Homan, Iriée Zamblé and Timothy Voges.

Other high-profile exhibits were Peter Vos: Metamorphosis (2016), Rembrandt's Naked Truth (2016), Glenn Brown (2017), Govert Flinck and Ferdinand Bol (2017–2018), HERE.