According to the World Health Organization (WHO), in 2016, nearly 2 billion adults were overweight, of which more than 650 million were obese [
1]. Obesity is common in both developed and developing countries, affecting all ages without distinguishing social classes [
2,
3]. Over the past 50 years, overweight and obesity have risen sharply. In 2016, the United Stated of America and Saudi Arabia registered the highest percentage of obese adults, 36.2% and 35.4%, respectively. Conversely, Vietnam, Japan, Ethiopia, and India had the lowest percentages of obese adults in 2016 [
1]. Overweight and obesity are defined as abnormal or excessive fat accumulation typically resulting in negative health impacts. Although there is a genetic predisposition to developing obesity, the causes of this disease are multifactorial. Thus, the complex interactions between epigenetics, lifestyle, cultural and environmental influences play a fundamental role in the development of obesity (
Figure 1) [
3,
4,
5]. Additionally, economic growth, social changes, and the global nutritional transition are seen as contributing to this epidemic [
6]. Obesity should not be seen only as a problem associated with physical image since people with excessive weight tend to have a higher risk of developing other comorbidities, such as type 2 diabetes, hypertension, and certain types of cancer, namely breast, ovary, liver, colon, and prostate [
2]. Obesity is also a risk factor for cardiovascular diseases, chronic respiratory diseases, and osteoarthritis, which contribute to more than half of all deaths. More serious cases of obesity are associated with an increasing incidence of diseases such as asthma, gallstones, steatohepatitis, glomerulosclerosis, dyslipidemia, and endothelial dysfunction [
7]. The list of health consequences is extensive, and in addition to affecting quality of life, it also contributes to a higher risk of premature death [
8]. In the last two decades, the need to develop new therapies increased significantly. The physiological treatment forces the patient to make changes in diet and behavior, which is not always feasible due to the patient’s lack of motivation. Thus, the pharmacological approach is more attractive. Currently, pharmacological therapy includes the use of synthetic drugs [
9], although the demand for natural substances that have fewer side effects is increasing. To determine the effectiveness of new drugs or promising natural compounds, these potential therapies must be first evaluated in preclinical models (in vitro and in vivo) and later clinically [
10]. Cell cultures are important for obtaining information on the pharmacodynamics of compounds; however, more complex interactions, which are those that contribute to the pathophysiology of obesity, are not noticeable. Therefore, preclinical models, specifically animal models, are essential for identifying and validating pharmacological targets [
11]. Animal models for studying obesity comprise a variety of species, from non-mammals (zebrafish,
Caenorhabditis elegans and
Drosophila) to mammals (rodents, large animals, and non-human primates) [
7]. Within these animal models, small rodents (rats and mice) are the most widely used. Their cost-effectiveness and multiparity, physiology close to humans, and easy genetic manipulation are some of the advantages that make them the model of excellence [
7]. In this review, we describe some of the most commonly used rodent models of research on obesity.