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Ethical requirements, severe constraints on access to end users and the necessity of real-world clinical evaluations represent significant challenges to designers of new technologies in mental healthcare (MHC) settings. This paper describes the collaborative approaches, incorporating HCI methods with input for MHC professionals and MHC theory, which were applied in the development of Personal Investigator (PI), a 3D computer game developed to support adolescent mental health interventions. Different stages in the evaluation of PI are discussed and the lessons learned through a multi-site clinical evaluation are presented. This evaluation has provided strong initial evidence that games such as PI offer the potential to improve adolescent engagement in talk-based interventions. It has also provided an insight into factors which should be considered in future designs in the MHC domain, e.g. the need to incorporate high levels of adaptability in future systems. Based on the difficulties encountered and lessons learned critical aims for future research are outlined.