The modern world faces an exploding obesity epidemic, and despite many years of intensive research, the current clinically available nonsurgical treatment strategies are rather unsuccessful and drugs that were expected to alleviate the obesity problem had to be withdrawn from the market. Hence, understanding the physiological controls of eating has never been more important; this understanding may potentially help to develop effective pharmacological tools that reduce eating and eventually body weight without unacceptable side effects. Obesity research has to a large extent been focused on central nervous system neurotransmitters and also on long-term adiposity signals; the controls of individual meals were less in that focus, but it is now recognized that adiposity signals influence eating by modulating the effect of meal size controls (e.g. Refs. 1 and 2). The effects of adiposity signals and meal size controls appear to exhibit sex differences, and at least in females, estradiol appears to be the major factor that is involved in the control of eating, mainly by modulating meal size controls (3–6). Basic research on the estrogenic inhibition of eating is of great health relevance. This research is expected to promote our understanding of disordered control of meal size in human eating disorders; women seem to be disproportionately more vulnerable to these disorders than men (7– 9). These disorders include anorexia nervosa, bulimia nervosa, and binge-eating disorder, which is an important contributor to obesity. Further, morbid obesity is more prevalent in women than men (10). Estradiol has been shown to control eating and body weight mainly via modulating the potency of feedback signals that control meal size (5, 6). The best investigated interaction is that between cholecystokinin (CCK) and estradiol; the data indicate that estradiol increases the satiating potency of exogenous and endogenous CCK (11– 13). Similar mechanisms may be operational for glucagon because the effects of glucagon and of glucagon antibodies to decrease or increase meal size, respectively, were both amplified by estradiol in ovariectomized (OVX) rats (14). Finally, our own unpublished data indicate that estradiol enhanced the acute eating inhibitory effect of exogenous amylin in OVX rats (Asarian L., N. Geary, and T. Lutz, unpublished observations). It is a well-established phenomenon that the absence of estradiol leads to a temporary increase in eating and a sustained increase in body weight (5, 9, 11). This phenomenon is of clinical relevance because estradiol levels decrease in postmenopausal women; importantly, postmenopausal women make up a high percentage of the obese population. Because most nonsurgical treatment options for obese people have been withdrawn from the market due to unacceptable side effects, the amylin-based combination therapy with leptin has raised increased interest as an effective antiobesity treatment. The recent paper by Trevaskis et al. (15) provides new and to a large extent surprising insight into the role of estradiol in the control of eating, in particular in terms of estradiol’s interaction with chronic amylin treatment. Trevaskis et al. used diet-induced obese (DIO) female rats that were OVX; part of the OVX rats received cyclic estradiol replacement that mimics the physiology of an intact female sexual cycle (16). Several key findings reported in this paper are worth mentioning here. Similar to previous studies in intact male DIO rats (17; see also Ref. 18), amylin reduced the body weight gain in sexually intact female sham-operated DIO rats. The effect was similar in OVX rats that received physiological estradiol replacement therapy; interestingly, amy-