BACKGROUND: The aim of the present study was to test if Antonovsky's theory of sense of coherence can facilitate understanding: (1). individual differences in psychological adaptation in parents of children with intellectual disability (ID); and (2). why parents of children with ID generally experience higher levels of stress and depression than parents of children who develop normally. METHODS: Sense of coherence (SoC) and depression were assessed using the short SoC scale (13 items) and the Beck Depression Inventory in 216 families of children with ID and/or autism, and in 213 control families. RESULTS: It is argued that: (1). parents of children with ID with low SoC are at increased risk for developing depression compared to control parents with low SoC not experiencing this stressor; and (2). the life situation of parenting a child with ID may have a negative impact on parents' SoC levels that, in turn, will make them more vulnerable to experiencing stress and depression. CONCLUSION: The SoC theory is valuable in understanding individual differences in psychological adaptation in parents of children with ID.