Research on mindfulness-based interventions (MBIs) for treating symptoms of a wide range of medical conditions has proliferated in recent decades. Mindfulness is the cultivation of nonjudgmental awareness in the present moment. It is both a practice and a way of being in the world. Mindfulness is purposefully cultivated in a range of structured interventions, the most popular of which is mindfulness-based stress reduction (MBSR), followed by mindfulness-based cognitive therapy (MBCT). This paper begins with a discussion of the phenomenological experience of coping with a chronic and potentially life-threatening illness, followed by a theoretical discussion of the application of mindfulness in these situations. The literature evaluating MBIs within medical conditions is then comprehensively reviewed, applying a levels of evidence rating framework within each major condition. The bulk of the research looked at diagnoses of cancer, pain conditions (chronic pain, low back pain, fibromyalgia, and rheumatoid arthritis), cardiovascular disease, diabetes, human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS), and irritable bowel syndrome. Most outcomes assessed are psychological in nature and show substantial benefit, although some physical and disease-related parameters have also been evaluated. The field would benefit from more adequately powered randomized controlled trials utilizing active comparison groups and assessing the moderating role of patient characteristics and program “dose” in determining outcomes.