Systematic reviews are being increasingly used to inform all levels of healthcare, from bedside decisions to policy-making. Since they are designed to minimize bias and subjectivity, they are a preferred option to assess the comparative effectiveness and safety of healthcare interventions. However, producing systematic reviews and keeping them up-to-date is becoming increasingly onerous for three reasons. First, the body of biomedical literature is expanding exponentially with no indication of slowing down. Second, as systematic reviews gain wide acceptance, they are also being used to address more complex questions (e.g., evaluating the comparative effectiveness of many interventions together rather than focusing only on pairs of interventions). Third, the standards for performing systematic reviews have become substantially more rigorous over time. To address these challenges, we must carefully prioritize the questions that should be addressed by systematic reviews and optimize the processes of research synthesis. In addition to reducing the workload involved in planning and conducting systematic reviews, we also need to make efforts to increase the transparency, reliability and validity of the review process; these aims can be grouped under the umbrella of 'modernization' of the systematic review process.