Children being raised by grandparents are one of the fastest growing groups of children in the United States and the world.  Most of the caregivers providing this “kinship care” are grandmothers. Often, the circumstances are borne out of complex life experiences such as parental illness especially HIV, child abuse and neglect, and maternal incarceration often related to drug and alcohol abuse. While there is a growing literature about custodial grandmothers, most studies are descriptive and atheoretical. There is a need for a theory depicting the issues and needs of custodial grandparents from an ecological holistic, developmental perspective.  Based on field notes, observations, focus group data, and questionnaires from our work with a community-based Grandparenting Program and a related self-care and parenting intervention, we developed a model based on Elder's Life Course perspective.  In this model, we consider the socio-cultural context and the life trajectory of the grandmother, her adult child, and the grandchild(ren) as these lives intersect to influence the challenges faced by grandmothers.  This includes the ongoing social and health problems of the adult child and the behavioral, health, and development problems of the grandchild(ren) who have been affected by the parents' lifestyle and problems.  Thus three major challenges face grandmothers: (a) dealing with her relationship with and feelings about her adult child; (b) managing the challenges of parenting the grandchild; and (c) meeting her own personal needs while caring for others.  This model depicting the “theory of the problem” provides a guide for interventions which must be aimed at all three challenges in order to reduce the stress of custodial grandparents, increase their effectiveness in parenting, and prevent adverse physical and emotional outcomes. The model has potential for intervening with custodial grandmothers in other parts of the world such as Africa.