Addressing spirituality in therapy is considered important by clients and therapists alike. However, practitioners report difficulties and confusion regarding how to work with spiritual difference, especially when clients’ spiritual beliefs are perceived as undermining their psychological well-being. The current study aimed to explore this challenge through the use of a qualitative design. Semi-structured interviews were conducted with 11 practitioners and transcripts were analysed using interpretative phenomenological analysis. Three superordinate themes were discerned in the data: Therapists' perception of clients' spiritual beliefs. Therapists' aims and responsibilities and Therapists' practice responses to psychologically unhelpful spiritual beliefs. When clients' spiritual beliefs were perceived as psychologically unhelpful, therapists experienced a conflict between their ethical stance to respect clients' beliefs and their aim to enhance psychological well-being. This conflict presented the greatest challenge for therapists working with different spiritual beliefs. Implications and recommendations for practice are considered and avenues for future research are highlighted.