In cells in general, regardless of their identity and functional status, the mediators of signal transduction (ST), the classic second messengers, are highly conserved: calcium, cAMP, nitric oxide, phosphorylation cascades, etc. At the same time, they are significantly less numerous than the extracellular signals (or first messengers) they represent, suggesting that this universal conversion of signals into second messengers follows the conventional rules of an organic code. Nevertheless, the way these second messengers are integrated and the consequences they trigger change dramatically according to cell organization – its structure and function. Here we examine ST beyond the generation of second messengers, and more as the ability of a cell in its different configurations to assign meaning to signals through discrimination of their context. In metabolism, cell cycle, differentiation, neuronal, and immune function the circuitry operating at cell level will proceed by the creation of conventional links between an increasing number of physiological activities, that is, changes in environment are progressively coupled to: transcription patterns; transcription and replication patterns; transcription, replication, and differentiation patterns; and transcription, replication, differentiation, and functional patterns.