Patients with cancer transitioning from completing their final cancer treatments to survivorship are particularly at risk for experiencing psychosocial stress, and the Institute of Medicine (IOM) has referred to these cancer patients as “lost in transition.” In this study, patients with cancer in their transition phase after completing their final radiation treatment were defined as cancer survivors (CS). CS must deal with chronic stressors such as the fear of cancer recurrence as well as the resumption of their roles in their family and work lives. Chronic stress impacts the nervous system and increases secretion of stress hormones (e.g. cortisol) from the endocrine system, which in turn influences immune function. These systems are particularly relevant for CS since research has shown associations between abnormal cortisol patterns and increased mortality in breast CS and immune dysfunction in CS can increase susceptibility to infections. The theoretical framework of psychoneuroimmunology (PNI), which describes the interactions between the psychosocial, neuroendocrine and immune systems, guided the choice of outcomes for this study. The IOM has identified a lack of theory-driven interventions for managing psychosocial stress in CS. We reviewed the literature and identified two major types of PNI-based psychosocial interventions for cancer patients, namely cognitive-behavioral and complementary medical. One promising brief and inexpensive psychosocial intervention was expressive writing, which involved participants disclosing their deepest thoughts and feelings regarding their cancer in four 20-30 minute writing sessions over four consecutive days. We conducted a two-arm randomized controlled trial to determine the efficacy of an online expressive writing (EW) intervention delivered to CS who were 2-12 months post-radiation treatment completion. The results of this study revealed that EW was effective in regulating stress in our sample of CS over a period of six weeks as measured by lowered salivary cortisol levels and lowered self-reported fear of cancer recurrence. Online EW is a low-cost and convenient approach for delivering stress-management interventions for CS during survivorship. However, coordinated efforts are needed from health researchers, professionals and policy makers to define standardized approaches for testing psychosocial interventions and using PNI biomarkers to help develop evidence-based psychosocial cancer-care for CS during survivorship.