Physiological cardiac hypertrophy (PCH), induced by intensive exercise or pregnancy, differs substantially from the pathological form of myocardial hypertrophy, accruing after aortic stenosis or chronic arterial hypertension. In contrast to pathological forms of cardiac hypertrophy, exercise-induced increase of left ventricular mass is related to cardiac myocytes enlargement, with no apparent sign of fibrosis or apoptosis, and does usually not result in cardiac failure. Recently published results obtained from various animal studies documented clear sex-specific regulation of exercise-induced cardiac hypertrophy in rodents, with a pronounced hypertrophic response to training load observed in female animals when compared to male littermate. In addition to increased cardiac hypertrophic response, females exhibited augmented lipolytic activity measured in adipose tissue in response to exercise, resulting in increased plasma free fatty acid levels, measured after training. Importantly, sex-specific differences in adipose tissue lipolysis and systemic fat metabolism induced by intensive training were also confirmed in human studies, performed on athletes and healthy volunteers. Since development of PCH during the physical training is accompanied by enhanced fatty acid oxidation and reduced glucose uptake, intensive lipolytic activity, measured in female adipose tissue could explain, at least in part, sex-specific differences observed in hypertrophic response to exercising. Given that sex hormones, such as estrogens and testosterone, in addition to their role in the regulation of adipose tissue metabolism, were also reported to modulate development of pathological myocardial hypertrophy, one may expect also a putative contribution of sex hormones in processes regulating the development and progression of PCH.