According to known laws of physics, chronic positive mass balance is the actual etiology of obesity, not positive energy balance. The relevant physical law in terms of body mass regulation is the Law of Conservation of Mass, not the Law of Conservation of Energy. A recently proposed mass balance model (MBM) describes the temporal evolution of body weight and body composition under a wide variety of feeding experiments, and it seems to provide a highly accurate description of the very best human experimental feeding data. By shifting to a mass balance paradigm of obesity, a deeper understanding of this disease may follow in the near future. The purpose of this article is to present the core issues of the upcoming paradigm shift as well as some practical applications related to the topic.