Objective This paper provides a review of key issues affecting the uptake of clinical guidelines by general practitioners (GPs) in Australia and internationally.Attention is given to the barriers that affect guideline uptake, the quality of guidelines and the dissemination of guidelines to GPs in practice settings. Method A comprehensive cross-disciplinary literature review of peer-reviewed journals was conducted between January and April 2008. The literature review was undertaken by three independent researchers from diverse disciplinary backgrounds. The review focused on studies that explored the barriers and issues associated with the use of guidelines in general practice and suggestions for more effective use. Results Pathways for clinicians to evaluate and use guidelines are still not clear. The majority of contemporary literature promotes linear 'uptake' and 'accessibility' models for clinical guidelines that may not attend to more complex issues associated with GPs' ways of practising on a daily basis. There are also few clear guidelines for GPs on how to 'adapt' guidelines for local and individual patient circumstances. Conclusions Peak organizations such as General Practice Queensland in Australia can have a significant role in helping GPs to evaluate and use clinical guidelines. The suggested approach emphasizes the need for such peak bodies to promote respect for practitioner experience, interpretation and patient insight.