This 2-year randomized trial of multiple sclerosis patients compared a coping skills group (n = 64) with peer telephone support (n = 68). Growth curve analyses that adjusted for neurological deterioration and gender revealed that the coping skills intervention yielded gains in psychosocial role performance, coping behavior, and numerous aspects of well-being. In contrast, the peer support intervention increased external health locus of control but did not influence psychosocial role performance or well-being. Subgroup analyses revealed that patients with affective problems were more likely to benefit from the peer support intervention than the coping skills group in terms of reported depression, anxiety, use of avoidant coping, and some aspects of well-being. The coping group is discussed as a vehicle for facilitating response shift, helping patients to change their internal referents, their conceptualization of quality of life, and their priorities.