General health implications of religiosity and spirituality on health have been associated with health promotion, so the purpose of this study was to examine the influence of religiosity and spirituality on rural parents' decision making to vaccinate their children against human papillomavirus (HPV). The associations of religiosity and spirituality with parental HPV vaccine decisions were examined in a sample of parents residing in small rural communities (N = 37). Parents of children aged 9 to 13 years participated in focus groups held in rural community contexts. Religiosity (ie, participation in religious social structures) was a recurring and important theme when discussing HPV vaccination. Spirituality (ie, subjective commitment to spiritual or religious beliefs) was found to influence the ways in which parents perceived their control over and coping with health issues potentially related to HPV vaccination. Together, religiosity and spirituality were found to play integral roles in these parents' lives and influenced their attitudes toward HPV vaccination uptake for their children.