Obesity is a worldwide epidemic, which is characterized by the excess accumulation of adipose tissue and to an extent that impairs both the physical and psychosocial health and well-being. There are several weight-loss strategies available, including dietary modification, pharmacotherapy, and bariatric surgery, but many are ineffective or not a long-term solution. Bioactive compounds present in medicinal plants and plant extracts, like polyphenols, constitute the oldest and most extensive form of alternative treatments for the prevention and management of obesity. Their consumption is currently increasing in the population due to the high cost, potential adverse effects, and limited benefits of the currently available pharmaceutical drugs. A great number of studies has explored how dietary polyphenols can interfere with the different mechanisms associated with obesity development. They suggest that these compounds can decrease energy and food intake, lipogenesis, and preadipocyte differentiation and proliferation, while increasing energy expenditure, lipolysis, and fat oxidation. Both quercetin, one of the most common dietary flavonols in the western diet, and epigallocatechin gallate (EGCG), the most abundant polyphenol in green tea, exhibit antiobesity effects in adipocyte cultures and animal models. However, the extrapolation of these potential benefits to obese humans remains unclear. Although quercetin supplementation does not seem to exert any beneficial effects on body weight, this polyphenol could prevent the obesity-associated mortality by reducing cardiovascular disease risk. An important consideration for the design of further trials is the occurrence of gene polymorphisms in key enzymes involved in flavanol metabolism, which determines a subject's sensitivity to catechins and seems, therefore, crucial for the success of the antiobesity intervention. Although the evidence supporting antiobesity effects is more consistent in EGCG than with quercetin studies, they could still be beneficial by reducing the cardiovascular risk of obese subjects, rather than inducing body weight loss.