Signalling concerns the transfer of information from one body, a source, to another, a receiver in order to stimulate activity. The problem arises with the word information. It is defined as what is transferred in a sequence of things, say between people, e.g. words or signs. The idea of signalling between people is then obvious but it is not clear in cell biology. Information transfer, signalling, is required for the organisation of all cellular activity but we must ask what is transferred and how is it transmitted and received? Sometimes it is assumed that all information, i.e. organisation in a cell, is represented in the DNA sequence. This is incorrect. We shall show that the environment is a second source of information concerning material and energy. The receiving party from both DNA and the environment is general metabolism. The metabolism then signals back and sends information to both DNA and uptake from the environment. Even then energy is needed with machinery to send out all signals. This paper examines the way signalling evolved from prokaryotes through to man. In this process the environmental information received increased to the extent that finally the brain is a phenotypic as much as a genotypic organ within a whole organism. By phenotypic we mean it is organised by and interactive with information from the environment.