Positions in a protein are thought to coevolve to maintain important structural and functional interactions over evolutionary time. The detection of putative coevolving positions can provide important new insights into a protein family in the same way that knowledge is gained by recognizing evolutionarily conserved characters and characteristics. Putatively coevolving positions can be detected with statistical methods that identify covarying positions. However, positions in protein alignments can covary for many other reasons than coevolution; thus, it is crucial to create high-quality multiple sequence alignments for coevolution inference. Furthermore, it is important to understand common signs and sources of error. When confounding factors are accounted for, coevolution is a rich resource for protein engineering information.