Protein engineering has been extensively applied to the development of genetically encoded reporters for spatiotemporally resolved monitoring of dynamic biochemical activity across cellular compartments in living cells. Genetically encoded reporters facilitate the visualization and recording of cellular processes, including transmission of signaling molecules, protease activity, and protein-protein interactions. In this review, we describe and assess common reporter motifs and protein engineering strategies for designing genetically encoded reporters. We also discuss essential parameters for evaluating genetically encoded reporters, along with future protein engineering opportunities in this field.