Many evolutionary applications in medicine rely on well-established methods, such as population genetics, phylogenetic analysis, and observing pathogen evolution. Approaches to evolutionary questions about traits that leave bodies vulnerable to disease are less well developed. Strategies for formulating questions and hypotheses remain unsettled, and methods for testing evolutionary hypotheses are unfamiliar to many in medicine. This article uses recent examples to illustrate successful strategies and some common challenges. Ten questions arise in the course of considering hypotheses about traits that leave bodies vulnerable to disease. Addressing them systematically can help minimize confusion and errors.