Systematic reviews and meta-analyses often occupy the top of the hierarchy of evidence in support of evidence-based clinical practice. These studies commonly inform the formulation of clinical guidelines. Bias can intrude at several levels during the conduct of systematic reviews. The effect these various biases, in particular reporting bias, have on pooled estimates and review inferences are potentially significant. In this review, we describe several forms of selection and reporting biases that may occur during the conduct of a systematic review, how these biases might affect a review and what steps could help minimize their influence on review inferences. Specifically, we support calls for prospective international trial registration and open access to trial protocols as two potential solutions that may improve the methodological quality of systematic reviews and the validity of their results. © 2006 Future Drugs Ltd.