Although genetics shapes our sense of taste to prefer some foods over others, taste sensation is plastic and changes with age, disease state, and nutrition. We have known for decades that diet composition can influence the way we perceive foods, but many questions remain unanswered, particularly regarding the effects of chemosensory plasticity on feeding behavior. Here, we review recent evidence on the effects of high-nutrient diets, especially high dietary sugar, on sweet taste in vinegar flies, rodents, and humans, and discuss open questions about molecular and neural mechanisms and research priorities. We also consider ways in which diet-dependent chemosensory plasticity may influence food intake and play a role in the etiology of obesity and metabolic disease. Understanding the interplay between nutrition, taste sensation, and feeding will help us define the role of the food environment in mediating chronic disease and design better public health strategies to combat it.