Steady advances in neuroscience have shaped understanding of brain and mind, in ways that challenge spiritual belief and can amplify misconceptions about biological determinism. The inability to reconcile spirituality and science risks faith being construed as “out of touch” with reality, and in worst-case scenarios engendering clinical-level crises of hope. The latter typically involve three central issues: the free will problem, desperate perceptions about mortality, and the constraint of individual identity. Here, we synthesize contemporary scientific and philosophical understanding to propose a reconciliation of faith and science of particular relevance to preservation of hope. In this approach, we review the compatibility of natural causation and human freedom, parameterize “meaning” on the basis of specific opportunities for decision-making within the timeframe of a lifetime, and articulate a model of self-transcendence predicated on these principles and on observed characteristics of human love. This model resides within “common ground” for faith and science by avoiding unnecessary dichotomization of the material and the Divine.