Prader–Willi syndrome is a complex genetic disorder involving a wide range of behavioral, psychiatric, neurocognitive, and medical problems. A review of existing research was presented to facilitate assessment work with this population. Hyperphagia, compulsions/repetitive behavior, self-injury (especially skin-picking), and aggressive behaviors are particularly common in people with Prader–Willi syndrome. Psychotic, affective, and obsessive–compulsive disorders represent the most frequently occurring psychiatric disorders. Assessment should involve consideration of how behavioral and psychiatric problems can be influenced by neurocognitive functioning and medical issues. Research findings in these areas are presented to help clinicians make comprehensive assessment of mental health problems. The heterogeneous and progressive nature of many behavioral and psychiatric problems in this population presents significant challenges to psychological assessment and management. Comprehensive assessment requires an understanding of the phenotype of Prader–Willi syndrome, and associated issues that can impact upon clinical presentation.