The present article reviews the relationship between sleep and oscillatory activity in Down Syndrome (DS), as well as the featuring emergent rhythmic activity across different brain states. A comprehensive discussion of the data from electroencephalographic studies in DS humans and transgenic/trisomic mouse models is provided, as well as data from signals collected from local field potentials (LFP) and intracellular recordings in DS mouse models. The first sections focus specially on the alpha phenotype consistently observed in DS subjects, as well as its description in DS childhood and aging. Subsequently, a review of the data reported in DS mouse models is presented with the aim to deepen on the mechanisms underlying altered rhythmic patterns. Further sections situate the state-of-the-art of the field, with a discussion on the possible circuit alterations that may underlie impaired alpha and gamma oscillatory activity. A further aim is to highlight the importance of studying network oscillatory activity in mouse models to infer alterations in the underlying circuits related to cognition, such as in intellectual disability. In this direction, a view of alpha and gamma rhythms generated by the cerebral cortex as a tool for evaluating an unbalance between excitation and inhibition in DS is claimed, which points out toward an over-inhibited network. A final aim is to situate oscillatory activity as a key phenomenon that may be used as a biomarker for monitoring as well the effect of novel therapeutic strategies.