Therapy games have the potential to offer people with disabilities a cost-effective, personalized, data-driven, connected, and motivating context for otherwise tedious and repetitive therapy. The paramount challenge in creating therapy games is creating a motivating experience with mechanics that translate into improved health outcomes---a wicked problem. To this end, I use research through design to explore multiple approaches to the co-creation of therapy games for various populations, including children with speech impairments, adults with developmental disabilities, children with Sensory-Based Motor Disorder (SBMD), and stroke survivors. I have collaborated on 3 therapy games, which serve as case studies where I explore identifying best practices, unique insights, and suggestions for future therapy game creators. Specifically, I discuss game-first versus therapy-first approaches, closed-game systems versus more open-ended playful systems, and potential future research directions.