Kinship, friendship alliances, and perceptions of others' beliefs guide social interactions and are central to cohesive group behavior. Under certain conditions, brain systems that involve regions along the frontal midline increase activity when inferences are drawn about others who share a similar view to one's own (similarity). A prominent hypothesis is that these regions contribute to social cognition by simulating the other person's perspective based on one's own experience. An alternative is that certain regions process the social relevance of the person (closeness) to oneself and contribute to the assessment akin to signals that govern behavioral approach responses. These alternatives were explored across four functional magnetic resonance imaging experiments (n = 98). Experiment 1 localized the target midline regions in the rostral anterior cingulate cortex and anterior medial prefrontal cortex by having participants make personal judgments. The two dimensions (similarity, closeness) were crossed in experiment 2 using actual friends of the participant and unknown others. Making judgments about oneself and friends resulted in increased midline response relative to unknown others regardless of whether the friends shared similar views as the participant. Experiment 3 revealed that similarity was not a factor even when close others were not included. Experiment 4 directly contrasted two extremes: participants made inferences about similar, unknown others and dissimilar friends. Judgments about the close others again increased blood oxygenation level-dependent response along the frontal midline. These results encourage further exploration of the idea that frontal systems linked with limbic circuits facilitate assessment of the relevance or personal significance in social contexts.