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Prevailing thinking about obesity and related diseases holds that quantifying calories should be a principal concern and target for intervention. Part of this thinking is that consumed calories – regardless of their sources – are equivalent; i.e. ‘a calorie is a calorie’. The present commentary discusses various problems with the idea that ‘a calorie is a calorie’ and with a primarily quantitative focus on food calories. Instead, the authors argue for a greater qualitative focus on the sources of calories consumed (i.e. a greater focus on types of foods) and on the metabolic changes that result from consuming foods of different types. In particular, the authors consider how calorie-focused thinking is inherently biased against high-fat foods, many of which may be protective against obesity and related diseases, and supportive of starchy and sugary replacements, which are likely detrimental. Shifting the focus to qualitative food distinctions, a central argument of the paper is that obesity and related diseases are problems due largely to food-induced physiology (e.g. neurohormonal pathways) not addressable through arithmetic dieting (i.e. calorie counting). The paper considers potential harms of public health initiatives framed around calorie balance sheets – targeting ‘calories in’ and/or ‘calories out’ – that reinforce messages of overeating and inactivity as underlying causes, rather than intermediate effects, of obesity. Finally, the paper concludes that public health should work primarily to support the consumption of whole foods that help protect against obesity-promoting energy imbalance and metabolic dysfunction and not continue to promote calorie-directed messages that may create and blame victims and possibly exacerbate epidemics of obesity and related diseases.