The article provides an overview of the current methodological landscape for analyzing drug combinations, focusing on both effect-based and dose-effect-based approaches. Effect-based strategies include the Combination Subthresholding, Highest Single Agent, Response Additivity, and Bliss Independence models, each with its own advantages and limitations. Dose-effect-based approaches, particularly Loewe Additivity, are more robust but require detailed dose-effect curves and can be complex to implement. The authors highlight six key issues in the analysis of drug combinations: the appropriate use of concepts and methods, the need for a standard reference analysis framework, adapting analysis methods to different stages of research and development, optimizing dose ratios, rigorous interpretation of results, and handling combinations of more than two drugs. They emphasize the importance of a multi-disciplinary approach and the need for more rigorous methodology to improve the quality and reproducibility of drug combination studies.The article provides an overview of the current methodological landscape for analyzing drug combinations, focusing on both effect-based and dose-effect-based approaches. Effect-based strategies include the Combination Subthresholding, Highest Single Agent, Response Additivity, and Bliss Independence models, each with its own advantages and limitations. Dose-effect-based approaches, particularly Loewe Additivity, are more robust but require detailed dose-effect curves and can be complex to implement. The authors highlight six key issues in the analysis of drug combinations: the appropriate use of concepts and methods, the need for a standard reference analysis framework, adapting analysis methods to different stages of research and development, optimizing dose ratios, rigorous interpretation of results, and handling combinations of more than two drugs. They emphasize the importance of a multi-disciplinary approach and the need for more rigorous methodology to improve the quality and reproducibility of drug combination studies.