The present paper briefly describes and contrasts two different motivations crucially involved in decision making and cooperation, namely fairness-based and compassion-based motivation. Whereas both can lead to cooperation in comparable social situations, we suggest that they are driven by fundamentally different mechanisms and, overall, predict different behavioral outcomes. First, we provide a brief definition of each and discuss the relevant behavioral and neuroscientific literature with regards to cooperation in the context of economic games. We suggest that, whereas both fairness- and compassion-based motivation can support cooperation, fairness-based motivation leads to punishment in cases of norm violation, while compassion-based motivation can, in cases of defection, counteract a desire for revenge and buffer the decline into iterative noncooperation. However, those with compassion-based motivation alone may get exploited. Finally, we argue that the affective states underlying fairness-based and compassion-based motivation are fundamentally different, the former driven by anger or fear of being punished and the latter by a wish for the other person's well-being.