Mathematical biologist Robert Rosen proposed a revolutionary new way of understanding life in terms of causal entailments and modelling relations, two main theory tracks in his work. His work, however profound in quality and elegant in explanation, remained incomplete during his lifetime and in need of synthesis. Such a synthesis was completed in 2011. The two main lines of reasoning were combined to define a new analytical methodology that is fully relational. This paper discusses the main implications of that synthesis, using the name R-theory to distinguish it from Rosen's original work. R-theory describes a fully closed causal unit of nature, called the holon, which is a Rosen modelling relation between category theoretic mappings (thus integrating both concepts). R-theory provides a new method of analysis that can relate whole and fractioned (mechanistic) aspects of nature. As such, it offers an approach for understanding complex phenomena at the edge of classical domains, which includes quantum, relativistic, living, social and cognitive phenomena. Copyright (c) 2012 John Wiley & Sons, Ltd.