This chapter argues when the children first begin to express sadness, explore the evidence for factors that promote children’s sadness and examine the relationship between the ordinary experience of sadness and children’s clinically significant depression. Expressions of sadness are the least common of infants’ expressions of emotion and, perhaps because they are relatively rare, it is not always easy for observers to distinguish sadness from other negative emotions. Infants may communicate their sadness vocally as well as through their facial expressions. Different patterns of brain activation are found when infants’ facial expressions of sadness are accompanied by full crying; sad expressions without crying are linked to activation of the left frontal lobe, but sadness that is accompanied by crying is associated with right frontal activation. Clinical depression is diagnosed on the basis of a complex set of symptoms that extend beyond the experience and expression of sadness.