Obesity and related co-morbidities are major health problems throughout the world. Dietary interventions are the most common strategies employed for weight loss in overweight and obese individuals. A large body of evidence has shown that many diets varying in quantity and quality of macronutrients are effective in promoting weight loss, but there is still extensive debate about what types of diet are most effective for treating overweight and obesity. Likewise, long-term weight loss and maintenance are difficult for overweight and obese people. On the other hand, significant inter-individual variation in weight loss in response to dietary composition has long been noted, partly accounted for by an individual’s genetic makeup. Identification of gene–diet interactions in weight loss may provide useful information for the development of personalized approaches to weight loss. This review summarizes dietary intervention studies for weight loss and maintenance, and recent studies of gene–diet interaction with regard to weight loss.