The influence of psychosocial factors on pain experience and patient response has received increasing interest and recognition. Patients with chronic pain from several sources (eg, musculoskeletal, cancer, or sickle cell) usually report that religiousness and spirituality are important in their lives. Prayer is the most used complementary therapy; religious coping is among the most common strategies used to deal with pain. Religious variables are not usually associated with pain measures, except in some studies indicating that petitionary prayer is related to higher pain levels, possibly suggesting a turning to religion due to increasing pain. The best available evidence supports a positive association between religiousness and spirituality, with higher well-being and positive affect, and a negative association with depressive and anxiety symptoms. We discuss the importance of addressing spiritual issues in clinical practice, and increasing and improving research on religiousness/spirituality in chronic pain patients.