Living cells are capable of extracting information from their environments and mounting appropriate responses to a variety of challenges. The underlying signal transduction networks enabling this response can be quite complex, and so sophisticated computational modeling coupled with precise experimentation is required to unravel them. Although we are still at the beginning of this process, some recent examples of integrative analysis of cell signaling are very encouraging. Quantitative models of signaling pathways (e.g. NF-kappaB) can be gradually constructed through continuous experimental validation, and important lessons can be learnt from such exercises.