RHT Edwards performed pioneering studies related to energy metabolism in human muscle. Using the needle biopsy technique the kinetics of phosphorylcreatine (PCr) breakdown and resynthesis were investigated in association with different types of exercise. An important finding was that resynthesis of PCr required ATP derived from oxidative phosphorylation emphasizing the interaction between aerobic and anaerobic processes. The classical role of PCr is seen as a reservoir of high-energy phosphates defending cellular ATP levels under anaerobic conditions, high rates of energy transfer or rapid fluctuations in energy requirement. Although the high concentration of PCr in glycolytic fast-twitch fibers may lend some support to a role of PCr as a temporal and spatial buffer of ATP, the primary importance of the creatine kinase reaction may in fact be to counteract large increases in ADP, which otherwise could be inhibitory to cellular ATPase mediated systems. A primary role in the maintenance of ADP homeostasis may explain why in many conditions there is an inverse relation between PCr and muscle contractility, whereas not between ATP and muscle contractility. The presence of the PCr/Cr system in cardiac tissue and brain seems redundant from a perspective of anaerobic energy provision. However, the presence of a mitochondrial isoform of creatine kinase and the findings that PCr/Cr has an important role in modulating oxidative phosphorylation demonstrate a crosstalk between aerobic and anaerobic energy systems. Besides its role in muscle energetic PCr/Cr has an important role in acid-base balance being the most important proton buffer in muscle. The work by RHT Edwards and others more than 30 years ago laid the foundation for the progress in our understanding of muscle energetics since when our view of the PCr/Cr system has changed from that of a simple equilibrium reaction to one with high complexity and diversity.