Unlike many of the other topics covered in this book, the difficulty in identifying conserved checkpoint genes lies more in choosing an appropriate method than in carrying out the work. Thus, this chapter concentrates more on the alternative strategies and under which circumstances the choice of a given method is appropriate. There are essentially three types of strategies for isolating conserved genes of any sort: through deoxyribonucleic acid (DNA)-sequence conservation, protein-structure conservation, and through functional conservation. Each of these approaches can be further subdivided into different techniques that could be applied, and the choice of technique is dependent on the system in which one is working and on the gene one is attempting to isolate.