In this interview, David Zierler, Oral Historian for AIP, L. Mario Amzel, Director of the Department of Biophysics and Biophysical Chemistry at Johns Hopkins. Amzel recounts his childhood in Argentina and discusses his developing interests in physics and thermodynamics as an undergraduate. He describes his graduate work in crystallography and liquid crystal displays under the direction of Leo Becka. Amzel describes the tumultuous political situation in Argentina and the impact these events had on his academic career, including his decision in 1967 to leave the country and continue his studies in Venezuela. He describes the circumstances leading to his decision to come to John Hopkins in 1969. Amzel describes the range of research projects he has worked on over the past fifty years, including his work on immunoglobulin and monoclonal antibodies, mitochondrial ATPase, leukotriene synthesis, and voltage-gated sodium channels. He explains the relevance of his work on various clinical and pharmacological therapies. Amzel emphasizes the importance and relevance of physics first principles in all of his work, and in particular statistical thermodynamics. He reflects on how his work sits at the nexus of physics, chemistry, and biology. At the end of the interview, Amzel describes the evolution of biophysics over the course of his career.