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Psychiatry has studied the effect on children of separation from their mothers or primary caregivers, but has not given equal attention to the effect on mothers of separation from their children. This article examines the current literature on separation from the mother's perspective. Following a review of the literature on mothers' attachment behaviors, as evidenced by separation from their very young children due to ordinary circumstances, attention will turn to specific populations of mothers enduring separation from their children in situations of hardship: mothers with mental illness, homeless mothers, mothers in prison, and two groups of working mothers—immigrant mothers and deployed navy mothers. Separation can be experienced as temporary, bringing on anxiety, or may involve a mother's choice between her child's safety and her own wish to keep the child near her, causing a conflict in the mother's feelings. In other situations, separation may be involuntary and long-lasting, inducing symptoms of depression, despair, and grief, all of which are characteristic of loss. The particular conditions of the separation—such as choice, control, and ongoing communication between mother and child—can mitigate the impact of the separation and transform it from a total to a partial loss. Three clinical cases of mothers forced to separate from their children in extreme circumstances are examined, with recommendations for treatment.