OBJECTIVES: Patient compliance and persistence to pharmacotherapies is important, especially in chronic conditions in inflammation and immunology (I&I) therapeutic area, to improve patient outcomes. Programs/interventions that aim at improving medication compliance and persistence play an important role in optimizing care. Since there is a lack of relevant systematic reviews in I&I, the objective of this study is to provide a comprehensive understanding of the effectiveness of compliance and persistence programs in the I&I therapeutic area. METHODS: A systematic literature search was conducted and studies were identified from PubMed, conference proceedings and grey literature. Selection criteria included studies published in English, German, Spanish, Italian and French languages between January 2008 and September 2013, that evaluated the impact of programs on medication compliance and/or persistence in I&I. Abstracts were screened by two researchers for inclusion, and discrepancy was resolved by a third researcher. Selected publications underwent full review and abstraction.  RESULTS: A total of 3,637 abstracts were screened, of which 29 evaluated the effectiveness of compliance and persistence programs. Studies reviewed covered different countries: the US (n = 19); Italy and the UK (n = 2 each); Australia, Denmark, Malaysia, and Poland (n = 1 each); multicenter (n = 1) and unreported/no country mentioned (n = 1).  The majority of patient programs were conducted in the osteoporosis disease area (n = 9), followed by inflammatory bowel disease (n = 4), and multiple sclerosis and ulcerative colitis (n = 3 each). The most effective interventions were one-on-one tailored counseling and web-based education/communications that improved medication compliance by 44% and 31%, respectively. Additionally, group-based motivational and problem-solving support resulted in improvement of 12% at 24 months. CONCLUSIONS: A well-developed compliance program can have a significant impact on improving patient compliance as well as persistence to therapies. This, in turn may improve patient outcomes.