This review provides an overview of the current methodological landscape for analyzing drug combinations. Drug combinations are increasingly used in medicine due to their potential for improved efficacy, reduced toxicity, and decreased development of drug resistance. However, the analysis of drug combinations remains challenging, with several methodological issues that need to be addressed. The paper discusses two main approaches for analyzing drug combinations: effect-based and dose-effect-based. Effect-based approaches compare the effect of a combination of drugs directly to the effects of individual drugs. Dose-effect-based approaches, such as Loewe Additivity, rely on the principle of dose equivalence and are based on the mathematical framework of Loewe Additivity. The Combination Index (CI) is a key measure used to assess the effect of drug combinations, with values less than 1 indicating synergy, values greater than 1 indicating antagonism, and values equal to 1 indicating additivity. The paper also highlights several issues in the analysis of drug combinations, including the need for appropriate use of concepts and methods, the need for a standard reference analysis framework, the need to adapt analysis to each step of the research and development process, the optimization of dose ratios, the need for more rigorous methodology, and the challenge of combining more than two drugs. The authors emphasize the importance of using appropriate methods and frameworks to ensure accurate and reliable analysis of drug combinations. They also highlight the need for further research and development in this area to improve the understanding and application of drug combination analysis.This review provides an overview of the current methodological landscape for analyzing drug combinations. Drug combinations are increasingly used in medicine due to their potential for improved efficacy, reduced toxicity, and decreased development of drug resistance. However, the analysis of drug combinations remains challenging, with several methodological issues that need to be addressed. The paper discusses two main approaches for analyzing drug combinations: effect-based and dose-effect-based. Effect-based approaches compare the effect of a combination of drugs directly to the effects of individual drugs. Dose-effect-based approaches, such as Loewe Additivity, rely on the principle of dose equivalence and are based on the mathematical framework of Loewe Additivity. The Combination Index (CI) is a key measure used to assess the effect of drug combinations, with values less than 1 indicating synergy, values greater than 1 indicating antagonism, and values equal to 1 indicating additivity. The paper also highlights several issues in the analysis of drug combinations, including the need for appropriate use of concepts and methods, the need for a standard reference analysis framework, the need to adapt analysis to each step of the research and development process, the optimization of dose ratios, the need for more rigorous methodology, and the challenge of combining more than two drugs. The authors emphasize the importance of using appropriate methods and frameworks to ensure accurate and reliable analysis of drug combinations. They also highlight the need for further research and development in this area to improve the understanding and application of drug combination analysis.