The fur is short, fine, and velvety in most species. The tail is strongly prehensile. There is no pouch. Most species are forest dwellers, but some occur on the Argentine pampas or in the Andes. The genus ranges vertically from sea level to about 3,400 meters.
Mouse opossums are nocturnal and usually arboreal, though some species are terrestrial.
They are often found on banana plantations and among small trees and vine tangles. They build nests of leaves and twigs in trees or shelter in abandoned birds' nests. They have also been located in ground nests, in holes in hollow logs, and under rocks. The species M. robinsoni does not seem to have a fixed abode but apparently spends the day in any suitable shelter when daylight overtakes it. This species reportedly is nomadic in Panama, occupying home ranges of about 0.22 ha.