Systematic reviews and meta-analyses of randomized trials have long been important synthesis tools for guiding evidence-based medicine. More recently, network meta-analyses, an extension of traditional meta-analyses enabling the comparison of multiple interventions, use new statistical methods to incorporate clinical evidence from both direct and indirect treatment comparisons in a network of treatments and associated trials. There is a need to provide education to ensure that core methodological considerations underlying network meta-analyses are well understood by readers and researchers to maximize their ability to appropriately interpret findings and appraise validity. Network meta-analyses are highly informative for assessing the comparative effects of multiple competing interventions in clinical practice and are a valuable tool for health technology assessment and comparative effectiveness research.