This qualitative study was nested within a trial of cognitive behaviour therapy (CBT) and supportive listening for patients with multiple sclerosis (MS). It aimed to enrich understanding of the changes made during therapy and to explore processes of change. In-depth interviews with 30 participants from the treatment trial were analysed inductively and five main themes were developed. The benefits that participants described experiencing as a result of the interventions were highly variable, idiosyncratic and often departed from outcomes measured within the trial. Tuning into and sharing one's thoughts and feelings and learning specific strategies for living with MS appeared to be important processes for change, and participants identified the latter as particularly important for sustaining long-term benefits from therapy. Whether participants fully engaged with the interventions appeared to be related to their perceptions of being the right sort of candidate for the intervention, their expectations and motivations, the therapeutic relationship, adequate tailoring of the intervention, and practical issues. This study builds on previous research on factors and processes involved in adjustment to MS, the benefits of CBT for this population and highlights important issues to consider when developing psychosocial interventions for people with MS.