Monoclonal antibodies (mAbs) have revolutionized the treatment landscape in many disciplines of human medicine. To continue this exciting trend, sustained identification of new, validated and preferably functional targets are needed. However, this is the precise bottleneck in today's development of the next generation of therapeutic mAbs. Failures in translating a target into a successful therapeutic mAb are much more frequent than successes. Labex MAbImprove is a French-led consortium of academic laboratories jointly working on several aspects of the development of next-generation mAbs. The network organizes annual international meetings gathering academia and industry to discuss the different challenges faced in the therapeutic mAbs field. The 2018 symposium (also called AIS2018 and co-organized with MabDesign, the immunotherapy French industrial sector) focused on the discovery and validation of new targets for therapeutic mAbs. Key players from industry and academia outlined a number of exciting contributions, notably dealing with new innovations in the target discovery area, but also lessons learned from failures in the past. This report summarizes the talks presented at the AIS2018. We aim at broad dissemination of the most relevant, unpublished findings presented during the meeting, and hope to inspire all the contributors in this field to take new directions and bring about improvements.