Fatigue is an extremely common side effect experienced during cancer treatment and recovery. Limited research has investigated strategies stemming from complementary and alternative medicine to reduce cancer-related fatigue. This research examined the effects of Reiki, a type of energy touch therapy, on fatigue, pain, anxiety, and overall quality of life. This study was a counterbalanced crossover trial of 2 conditions: (1) in the Reiki condition, participants received Reiki for 5 consecutive daily sessions, followed by a 1-week washout monitoring period of no treatments, then 2 additional Reiki sessions, and finally 2 weeks of no treatments, and (2) in the rest condition, participants rested for approximately 1 hour each day for 5 consecutive days, followed by a 1-week washout monitoring period of no scheduled resting and an additional week of no treatments. In both conditions, participants completed questionnaires investigating cancer-related fatigue (Functional Assessment of Cancer Therapy Fatigue subscale [FACT-F]) and overall quality of life (Functional Assessment of Cancer Therapy, General Version [FACT-G]) before and after all Reiki or resting sessions. They also completed a visual analog scale (Edmonton Symptom Assessment System [ESAS]) assessing daily tiredness, pain, and anxiety before and after each session of Reiki or rest. Sixteen patients (13 women) participated in the trial: 8 were randomized to each order of conditions (Reiki then rest; rest then Reiki). They were screened for fatigue on the ESAS tiredness item, and those scoring greater than 3 on the 0 to 10 scale were eligible for the study. They were diagnosed with a variety of cancers, most commonly colorectal (62.5%) cancer, and had a median age of 59 years. Fatigue on the FACT-F decreased within the Reiki condition (P=.05) over the course of all 7 treatments. In addition, participants in the Reiki condition experienced significant improvements in quality of life (FACT-G) compared to those in the resting condition (P <.05). On daily assessments (ESAS) in the Reiki condition, presession 1 versus postsession 5 scores indicated significant decreases in tiredness (P <.001), pain (P <.005), and anxiety (P<.01), which were not seen in the resting condition. Future research should further investigate the impact of Reiki using more highly controlled designs that include a sham Reiki condition and larger sample sizes.