Oxytocin (OT) matters for social functioning, and optimal evaluations of therapeutic efficacy matter for individuals with psychiatric and neurodevelopmental disorders. Recently, Guastella and Hickie (1), experts in the field of autism therapeutics, provided a comprehensive review of the potential of OT for improving social cognition in patients with autism spectrum disorder (ASD) and emphasized the need for better approaches to evaluate OT therapies in clinical settings. The ancient 500 million-year-old OT system has undergone tremendous physiologic transformations in neuronal morphology, axonal projections, and receptor distribution in the brain to shape species-specific social features, such as maternal motivation, pair bonding, and social learning (2). By using pharmacologic approaches and transgenic mice with mutations in the genes encoding OT or its receptor, researchers refined the role of OT in social information processing and social recognition (3). In recent decades, OT has become the sweetheart of social neuroscientists because of its effects on social behavior and its potential for enhancing social skills in individuals with psychiatric disorders. Long-term administration of OT to individuals with ASD was recently shown to be safe and to increase social reciprocity (4,5) and eye gaze (4). These behavioral improvements were associated with increased functional connectivity between anterior cingulate cortex and dorsomedial prefrontal cortex (4), which is known to be significantly altered in ASD. These promising findings are in agreement with the recent discovery that long-term intranasal administration of OT restored social behavior in a mouse model of autism (6). The key challenge in intranasal OT research is to translate optimistic research findings into potential therapies yielding sustainable improvements in social functioning in individuals with ASD.