Psychological diagnosis faces unique challenges when used to differentiate nonpsychopathological religious/spiritual/transpersonal (R/S/T) experiences from those that might evidence psychopathology, particularly considering the diversity of such experiences and the value-laden assumptions inherent in most diagnostic practices. Theoretical and pragmatic problems related to the diagnostic category, Religious and Spiritual Problem, as contained in the Diagnostic and Statistical Manual of Mental Disorders are discussed. Attention is paid to identifying potential biases and errors in using, or failing to use, this diagnostic category, particularly as related to developing culturally sensitive diagnoses. Specific methods, including psychometric approaches, for evaluating R/S/T experiences that may range from healthy to psychopathological are reviewed and recommendations are presented for improving current diagnostic practices and furthering needed research.