Networks of randomized clinical trials can be evaluated in the context of a network meta-analysis, a procedure that permits inferences into the comparative effectiveness of interventions that may or may not have been evaluated directly against each other. This approach is quickly gaining popularity among clinicians and guideline decision makers. However, certain methodological aspects are poorly understood. Here, we explain the geometry of a network, statistical and conceptual heterogeneity and incoherence, and challenges in the application and interpretation of data synthesis. These concepts are essential to make sense of a network meta-analysis.