Synthetic biology often takes cues from complex natural networks and pathways to create novel biological systems. The design modalities used in synthetic systems generally follow the different classes of gene regulation in cells such as transcriptional, post-transcriptional and post-translational regulation. The latter class is most prominent in cell signaling pathways that operate via multitude of protein---protein interactions. Engineering signaling pathways is a relatively unexplored area. This review discussed the work toward signaling pathway engineering in diverse biological contexts including bacteria, yeast, vertebrate, and plant cells. While creating synthetic signaling cascades is perhaps one of the most challenging tasks in synthetic biology, potential implications can be far-reaching and include new tools for programming cells and tissues, artificial developmental processes, and therapeutic tools.