Developing combinations of therapeutic agents is an important strategy in the development of effective treatment. In the clinical area, methods for combinations are well-characterized, but what of the evaluation of combination in the preclinical or discovery stage of development? In the search for efficacious treatments, efficacious combinations can be evaluated long before the clinical stage. Characterizing the efficacy of single compounds in discovery and preclinical stage experiments is a relatively well-defined exercise. Combination experiments at the same stage pose additional considerations. In vitro experiments must examine appropriate assumptions around: design with regards to titrations, appropriate null models, impact of non-parametric vs parametric determination of deviance from the null model, and potential for timecourse experiments. In vivo experiments play a key role in translational research and might be approached in ways mirroring clinical designs. This roundtable will discuss pros, cons, and experiences with the above as well as the additional experience and expertise of the participants.