Recent brain imaging studies have shown that the neural substrates underlying the ability to infer and share the feeling of pain of other individuals overlap with the pain matrix that mediates the process of one's own pain. While there has been evidence that the neural activity mediating pain experience is influenced by top-down attention, it remains unclear whether the neural substrates of empathy for pain are modulated by top-down controlled mechanisms. The current work investigated whether the neural correlates of empathic processes of pain are altered by task demand and prior knowledge of stimulus reality. Subjects were scanned using functional magnetic resonance imaging (fMRI) while watching pictures or cartoons of hands that were in painful or neutral situations. Subjects were asked either to evaluate pain intensity supposedly felt by the model or to count the number of hands in the stimulus displays. Relative to counting neutral stimuli, rating pain intensity of painful pictures and cartoons induced increased activation in ACC/paracingulate and the right middle frontal gyrus. Rating pain intensity also activated the inferior frontal cortex bilaterally and the right insula/putamen for pictures but activated the left parietal cortex, the postcentral gyrus, and the occipito-temporal cortex for cartoons. However, the neural activities related to pain rating were eliminated when subjects counted the number of hands in the painful stimuli. In addition, the ACC activity associated with empathy for pain was stronger for the pictures than for the cartoons. Our findings indicate that the involvement of the neural substrates underlying pain-related empathy is constrained by top-down attention and contextual reality of stimuli.