Between 1828 and 1838 Johannes Muller (1801-1858) published his important neurophysiological and anatomical investigations (primary fibres, cranial nerves, reflex movement, experimental proof of Charles Bell's law). Muller's strategies and concepts in neurophysiology can be used as an example for his scientific approach. An analysis of the four editions of Muller's Handbook of Physiology shows that he specified his arguments continuously by introducing clear definitions of physiological terms (stimulus, excitability, cosensual movement, reflex), which were based on his own manifold experiments and a critical review of recently published researches. Following his own epistemological view of physiological sciences he changed his fundamental belief in the incompatibility of the force of nerves and physical electricity in regard to Du Bois-Reymond's electrophysiological investigations. Muller's strategy in explaining scientific problems provides information for a historical understanding of why he had such a great influence on the development of physiology, anatomy and marine biology in the 19th century.