This study examined the relationship between spirituality, medical access and support, social support and involvement, perceived severity of illness, illness status and resilience (i.e., self-reliance, equanimity and meaningfulness) in multiple sclerosis (MS). The sample consisted of 152 individuals diagnosed with relapsing-remitting MS who were either attending a neurology clinic, members of the National MS Society or members of a support group in the Northern Virginia, Washington DC area. Participants completed the Contributing Factors Questionnaire (CFQ), the Resilience Scale (RS), and the Spiritual Perspective Scale (SPS). The results indicated that individuals who had attributed higher rates of importance to medical access and support from doctors and nurses had an increased awareness that their lives had purpose and meaning. Furthermore, perceived severity of illness was significantly negatively related to self-reliance; those individuals who had a more severe perception of illness had a decreased belief in themselves and their capabilities. There was also a significant interaction effect between perceived severity of illness and spirituality on self-reliance and meaningfulness. That is, individuals with a more severe perception of illness who had higher levels of spirituality reported increased belief in themselves and their capabilities and an increased awareness that their lives had purpose and meaning. In addition, there was a significant interaction effect between illness status and spirituality on self-reliance and meaningfulness. That is, those individuals experiencing a relapse with higher levels of spirituality reported an increased belief in themselves and their capabilities and an increased awareness that their lives had purpose and meaning. There was neither a statistically significant relationship between spirituality, illness status and self-reliance, equanimity and meaningfulness nor between social support and involvement and self-reliance, equanimity and meaningfulness. There was not a significant relationship between medical access and support and self-reliance and equanimity. There was not a significant relationship between perceived severity of illness and equanimity and meaningfulness. There was not a significant relationship between spirituality and self-reliance, equanimity and meaningfulness after controlling for other contributing factors. There was not a significant interaction effect between perceived severity of illness and spirituality and between illness status and spirituality on equanimity.