As a result of its expansion during obesity, white adipose tissue undergoes structural and functional changes that contribute to an increased risk of developing diabetes or cardiovascular disease, and premature death. Compelling evidence suggests that the quality of some energy nutrients can modulate the physiological response to a positive energy balance. Indeed, the quality of dietary fatty acids can modulate numerous biological functions and slow down or prevent some pathologies. Studies have highlighted the health benefits of omega-3 polyunsaturated fatty acids, particularly regarding adipose tissue functions during obesity and against related co-morbidities. In connection with changes in the fatty acid profile of diets that may have contributed to the rise in obesity prevalence in Western countries, this article describes how omega-3s can modulate the accumulation and function of the adipose tissue. It was prepared based on human observational data, preclinical and clinical intervention data, and cellular models.