The free-energy principle states that all systems that minimize their free energy resist a tendency to physical disintegration. Originally proposed to account for perception, learning, and action, the free-energy principle has been applied to the evolution, development, morphology, anatomy and function of the brain, and has been called a postulate , an unfalsifiable principle , a natural law , and an imperative . While it might afford a theoretical foundation for understanding the relationship between environment, life, and mind, its epistemic status is unclear. Also unclear is how the free-energy principle relates to prominent theoretical approaches to life science phenomena, such as organicism and mechanism. This paper clarifies both issues, and identifies limits and prospects for the free-energy principle as a first principle in the life sciences.