Background: The objective of this study is to explore experiences of Czech mothers caring for children with profound intellectual and multiple disabilities. Methods: Semistructured interviews combined with biographical narration of mothers of children with profound intellectual and multiple disabilities and a short questionnaire for demographic data were used for data collection. Data analyses were carried out according to Van Manen's approach, including defining the main themes and description of the lived experiences of mothers. Findings: The dominant themes that emerged from the interviews were (1) losses and limits, (2) increased demands and exhaustion, (3) worries, (4) challenges connected to help and support, (5) transformation, (6) pleasures with contentment of the child and a small development and (7) functional support. Conclusions: The findings demonstrate that mothers of children with profound intellectual and multiple disabilities are at risk of facing many kinds of life difficulties, but the children have also positive impact on the mothers' lives. Relevant professionals and policy makers should be aware of the needs and challenges experienced by this vulnerable population.