Astrocytes are an abundant and evolutionarily conserved central nervous system cell type. Despite decades of evidence that astrocytes are integral to neural circuit function, it seems as though astrocytic and neuronal biology continue to advance in parallel to each other, to the detriment of both. Recent advances in molecular biology and optical imaging are being applied to astrocytes in new and exciting ways but without fully considering their unique biology. From this perspective, we explore the reasons that astrocytes remain enigmatic, arguing that their responses to neuronal and environmental cues shape form and function in dynamic ways. Here, we provide a roadmap for future experiments to explore the nature of astrocytes in situ.