Various challenges currently impede advanced AI technologies from directly benefiting society. The HI Research Unit at DKFZ pioneers research in three focus areas to address these challenges: 1) Advance to a deeper understanding and generalizability of algorithms (Focus Area Image Analysis), 2) Consider humans as an integral part of AI-application to enable reliable and safe deployment (Focus Area Human-Machine Interaction), and 3) Lead initiatives towards standardizing evaluation and benchmarking practices in the field and develop user-friendly tools to guide the community (Focus Area Validation Benchmarking).