BACKGROUND: People with chronic diseases experience barriers to managing their diseases and accessing available health services. Patient navigator programs are increasingly being used to help people with chronic diseases navigate and access health services. OBJECTIVE: The objective of this review was to summarize the evidence for patient navigator programs in people with a broad range of chronic diseases, compared to usual care. METHODS: We searched MEDLINE, EMBASE, CENTRAL, CINAHL, PsycINFO, and Social Work Abstracts from inception to August 23, 2017. We also searched the reference lists of included articles. We included original reports of randomized controlled trials of patient navigator programs compared to usual care for adult and pediatric patients with any one of a defined set of chronic diseases. RESULTS: From a total of 14,672 abstracts, 67 unique studies fit our inclusion criteria. Of these, 44 were in cancer, 8 in diabetes, 7 in HIV/AIDS, 4 in cardiovascular disease, 2 in chronic kidney disease, 1 in dementia and 1 in patients with more than one condition. Program characteristics varied considerably. Primary outcomes were most commonly process measures, and 45 of 67 studies reported a statistically significant improvement in the primary outcome. CONCLUSION: Our findings indicate that patient navigator programs improve processes of care, although few studies assessed patient experience, clinical outcomes or costs. The inability to definitively outline successful components remains a key uncertainty in the use of patient navigator programs across chronic diseases. Given the increasing popularity of patient navigators, future studies should use a consistent definition for patient navigation and determine which elements of this intervention are most likely to lead to improved outcomes. TRIAL REGISTRATION: PROSPERO #CRD42013005857.