Background: There is an emerging literature on the existence and effect of industry relationships on physician behavior. Little is known, however, about the effects of these relationships and conflict of interest (COI) on clinical practice guideline (CPGL) development and recommendations. Objectives: To perform a systematic review of the financial relationships and COI between CPGL authors and industry and to evaluate the effects of these relationships on CPGL recommendations. Methods: We searched Medline (1980 to March, 2010) for studies that examined the effect of COI on the development and/or conclusions of CPGL. Two reviewers independently identified potential studies from the literature search and data abstraction was reviewed by a second author. We performed a narrative synthesis as there was substantial heterogeneity among studies. Results: Ten studies fulfilled inclusion criteria; 8 were conducted in the US. All studies reported on financial relationships of CPGL authors and the pharmaceutical industry; 1 study also examined COI with diagnostic testing and insurance companies. The majority of guidelines have authors with industry affiliations. Nine studies categorized financial relationships: consultancies (8 studies, % of authors with relationship, range 1 80%); research support (8 studies, range 4 78%); equity/stock ownership (5 studies, range 2 17%); any COI (3 studies, range 56 87%). Four studies reported multiple types of financial interactions for individual authors (number of categories per author: range 2 to 10 or more). Five studies described a potential effect of COI on the CPGL; in 4 studies the evidence did not support the CPGL conclusions and the guideline authors had financial ties that benefited from the conclusions. Most authors believed that their relationships did not influence their recommendations. Conclusions: Few studies describe or quantify the effects of financial relationships on the development and/or recommendations of CPGLs and further research is needed to explore and quantify this important source of bias.