Protein tyrosine phosphatases (PTPs) play vital roles in numerous cellular processes and are implicated in a growing number of human diseases, ranging from cancer to cardiovascular, immunological, infectious, neurological and metabolic diseases. There are at least 107 genes in the human genome, collectively referred to as the human 'PTPome'. Here the authors review the involvement of PTPs in human disease, discuss their potential as drug targets, and current efforts to develop PTP inhibitors for the treatment of human disease. Finally, the authors present their view of the future for PTPs as drug targets.