Using the Stetler model, in-depth literature reviews were performed that demonstrated a positive correlation between humor and comfort levels in patients with cancer. Humor frequently was used for relaxation and as a coping mechanism that aided in promoting general wellness. The literature indicated that various types of humorous material lessened anxiety and discomfort, which allowed for patients' concerns and fears to be discussed openly. The literature also showed that humor had a positive effect on the immune system. Improvements in pain thresholds and elevations in natural killer cell activity consistently appeared in quantitative experimental studies. In addition, measurements of specific neuroendocrine and stress hormone levels revealed biochemical changes that suggested improved physical stress responses and increased feelings of well-being after humorous interventions. This article has implications for nurses because humor can be an effective intervention that impacts the health and well-being of patients with cancer.