Through studies in mammalian model systems, the estrogen-receptor-related receptor (ERR) alpha, an orphan nuclear receptor, has been shown to interfere with estrogen signaling and might therefore be an interesting pharmaceutical target in estrogen-related diseases. ERRalpha is also involved in energy storage and consumption, and its modulation might be of relevance in the treatment of obesity and diabetes. Recent data have also been published on the effects of this receptor, as well as other members of the ERR family, in non-mammalian animal model systems. Besides indications concerning their mechanisms of action, this analysis demonstrated a role for ERRalpha in controlling cellular movements, and suggested that ERRs might be implicated in a more subtle range of processes than originally envisioned.