Research shows convincingly that patients with serious medical illnesses commonly use spiritual methods to cope with and manage their illnesses. This reliance on spirituality seems to be associated with a range of positive outcomes in the form of an enhanced sense of well-being, improved feelings of resiliency, and decreased adverse physical symptoms (e.g., pain and fatigue) and psychologic symptoms (e.g., anxiety). The methodologic flaws and limitations of this literature, however, make more research necessary before confident conclusions can be made regarding the objective, biologic benefit. Further efforts should focus on identifying the potential mechanisms through which spirituality enhances both subjective and objective outcomes. Care should be taken to use reliable, valid spirituality assessment measures and more advanced methodologic designs, such as prospective, longitudinal studies, and randomized, controlled trials.