BACKGROUND Patients with head and neck cancer often face a plethora of cancer and treatment-related side effects, negatively impacting their lean body mass, physical functioning, quality of life and fatigue management. Physical activity is a potential mediator of many of these side effects. This is the first systematic review reporting on head and neck cancer and physical activity literature. METHODS A literature search was conducted up to January 2015. Two reviewers independently identified articles using the outlined inclusion criteria, assessing the study methodology, risk of bias and extracting the necessary data from studies evaluating the impact of full-body physical activity on patients with head and neck cancer. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement was used to guide this review. RESULTS We identified 16 articles published from 2003 to 2014, the majority of which were published within the past 5 years. Physical activity interventions were feasible, safe and beneficial in mediating cancer and treatment-related side effects. Specifically, patients experienced improvements in lean body mass, muscular strength, physical functioning, quality of life and fatigue management. Owing to significant study heterogeneity, data were not pooled. Reflecting the early state of the literature, included studies were found to vary greatly in design, quality and reporting characteristics. CONCLUSIONS There is early evidence that supports the benefit of physical activity interventions for patients with head and neck cancer, both during and following treatment. Future research is necessary to determine the benefits of different physical activity interventions, and their impact on patients with different head and neck cancers.