The aim of this systematic review was to synthesize the best available evidence informing the effectiveness of non-pharmacological interventions for managing cancer-related fatigue in men treated for prostate cancer. This review considered experimental studies that included men with prostate cancer (regardless of staging, previous treatment or comorbidities), aged 18 years and over who were undergoing any treatment, or had completed any treatment for prostate cancer within the previous 12 months. Three interventions were identified for the management of cancer-related fatigue in men with prostate cancer. Evidence from five studies including 447 participants demonstrates the effectiveness of physical activity, both aerobic and resistance exercise, and from three studies including 153 participants suggesting the benefits of psychosocial interventions including education and cognitive behavioural therapy. Health professionals require knowledge of a range of effective interventions aimed at reducing cancer-related fatigue in men with prostate cancer and should incorporate those interventions into their patient management. Although physical activity appears to show the greatest benefit, other non-pharmacological interventions such as education and cognitive behavioural therapy have demonstrated benefit and should also be considered as a strategy in treating this debilitating side effect of cancer and its treatment.