About 30% of human proteins contain covalently bound phosphate, and 500 protein kinases and a third that number of protein phosphatases are encoded by the human genome. In view of this, it is not that surprising that abnormal phosphorylation should turn out to be a cause or consequence of human disease. A number of diseases that result from mutations in particular protein kinases and phosphatases are listed in Table 1. However, many naturally occurring toxins and pathogens also exert their effects by altering the phosphorylation states of proteins. For example, some years ago Jack Dixon discovered that a major virulence factor of Yersinia is a protein tyrosine phosphatase [1]. This class of bacteria causes several serious diseases, including the bubonic plague, which has been responsible for many pandemics over the past millennium. These include the Black Death, which killed 25% of the population of Europe (42 million people) in the 12th and 13th centuries. This phosphatase can enter human cells causing uncontrolled dephosphorylation of many tyrosine residues that rapidly proves fatal