Signal transduction by protein phosphorylation represents one of the most prevalent mechanisms by which eukaryotic cellular events are regulated. It is involved in the control of many physiological processes and pathological conditions including bacterial and viral diseases. Emphasis will be placed on cellular regulation by tyrosine phosphorylation implicated in cell growth, differentiation and transformation, bringing into play a diversity of tyrosine kinases of viral or cellular origin or linked to growth factor receptors. These receptors transduce their signal by recruiting adaptor proteins interacting with one another through binding modules (SH2, SH3, WW, PH, PDZ, etc.) thereby initiating a diversity of signaling cascades. Examples decribing how a few of these are utilized will be presented. Regulation of signal transduction also involves protein tyrosine phosphatases (PTPs), an expanding family of transmembrane and intracellular enzymes that catalyze the reverse reaction. Most PTP receptor forms have the structural characteristics of cell adhesion molecules which suggests that they must be involved in – or be regulated by – cell-cell or cell-matrix interaction. Their involvement in oncogenesis will be presented. In contrast to the old view when metabolic pathways were represented by simple linear arrays of enzymes working successively on one another, we know today that cell signaling brings into play entire networks of enzymes, receptors and channels, a plethora of sub-cellular elements plus environmental factors such as the scaffolding proteins, chaperones, targeting subunits etc., all interacting and communicating with one another. We must comprehend the cross-talk that takes place among all these elements if we really want to understand how the cell functions. Only then will we be able to embark on a rational approach to therapeutics.