Several sleep disorders are caused by the disruption of the circadian clock, which is underpinned by the fluctuating activity of transcription factors that periodically inhibit their own expression. The nuclear receptor REV-ERBα, which is activated by heme binding, stabilises the clock by repressing Bmal1 transcription – but could REV-ERBα be a good pharmacological target for circadian-rhythm disorders? On page 3629, Andrew Loudon and colleagues propose that it could. The authors use a FRET-based in vitro screen to identify a compound that promotes the formation of a complex between REV-ERBα and the nuclear receptor co-repressor (NCoR). In fibroblasts expressing Bmal1 or Rev-erba, they show, the expression level of both genes oscillates. Importantly, the addition of the REV-ERBα ligand causes phase shifts in BMAL1 and PER2 activity that change their directionality according to the phase of the circadian clock. Moreover, phase-dependent phase resetting also occurs in lung slices treated with the REV-ERBα ligand. The authors propose that the binding of REV-ERBα to endogenous ligands, such as heme, might be a mechanism of clock resetting; moreover, pharmacological modulation of REV-ERBα might offer a novel approach to the treatment of circadian-rhythm disorders.