Living with a long-term health condition can lead to anxiety, depression, posttraumatic stress disorder, and relationship difficulties. This article uses a systematic case study approach to examine the process and outcome of transactional analysis psychotherapy with a woman suffering from multiple sclerosis. Hermeneutic analysis of a rich case record was used to evaluate the outcome of the intervention. A set of factors contributing to change were identified and are discussed in relation to previous research into psychotherapy for long-term health conditions. It is concluded that transactional analysis psychotherapy may represent an effective means of allowing different facets of the experience of illness to be explored and resolved. The implications of this study for practice and future research are discussed.