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. Keywords Adaptation • Free energy • Life • Mechanism • Organicism 1 Introduction According to the free-energy principle (FEP), all systems that minimize their free energy resist a tendency to physical disintegration. Originally proposed to explain how sensory cortex infers the causes of its inputs and learns causal regularities, FEP has been used to elucidate the function of action, perception, and attention, and to account for organisms' evolution and development (