The levels of tyrosine phosphorylation required for cell growth and differentiation are achieved through the coordinated action of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Depending upon the cellular context, these two types of enzymes may either antagonize or cooperate with each other during the signal transmission process. An imbalance between these enzymes may impair normal cell growth, leading to cellular transformation. Both PTKs and PTPs have evolved to a level of structural diversity that allows them to regulate many cellular processes. This review will focus on several specific examples that highlight the interplay between PTPs and PTKs in cell signaling.