People who have recently been diagnosed with a life-threatening or life-altering condition frequently report an intense search for meaning—a search for some reason or understanding for why they have developed the condition (e.g., “Why me?”), and what implications it has for one’s sense of self, one’s goals, and one’s understanding of how the world works. In this chapter, we explore what this search entails, what it indicates, and how people have found answers to these meaning questions. We conclude with some discussion of therapeutic interventions that may help individuals resolve these meaning issues.