Background: Patient navigation refers to a direct patient care role that links patients with clinical providers and their support system and provides individualized support during cancer care, ensuring that patients have access to the knowledge and resources necessary to complete recommended treatment. While most reports have studied the role of patient navigators during the cancer screening or diagnostic process, emerging evidence indicates the benefits of patient navigation during active cancer treatment. Discussion: Reports in the literature are conflicting on the impact of patient navigation during cancer care and on the benefits to timely or quality care in all populations. Recent sub-analyses of the Patient Navigation Research Program data demonstrated specifically the benefits of targeting patient navigation to the most vulnerable populations, including those with low educational attainment, low income and unstable housing, less social support, multiple comorbidities, and minority race/ethnicity. Conclusion: The implications of the Patient Navigation Research Program are that this resource is best utilized when directed to support the care of patients at locations with known challenges to timely care and for specific patients with risk factors for delays in care, including comorbidities, low educational attainment and low income. Implementation of patient navigation programs requires the following processes: needs assessment, selection of a navigator to meet the community and care needs, supervision and integration of the navigator into clinical processes, and systems support to facilitate the identification and tracking of those patients requiring patient navigation. There is a need for ongoing research on methods to fund and sustain patient navigation programs.