Introduction: In multi-objective drug design, optimization gains importance, being upgraded to a discipline that attracts its own research. Current strategies are broadly classified into single – objective optimization (SOO) and multi-objective optimization (MOO).

Areas covered: Starting with SOO and the ways used to incorporate multiple criteria into it, the present review focuses on MOO techniques, their comparison, advantages, and restrictions. Pareto analysis and the concept of dominance stand in the core of MOO. The Pareto front, Pareto ranking, and limitations of Pareto-based methods, due to high dimensions and data uncertainty, are outlined. Desirability functions and the weighted sum approaches are described as stand-alone techniques to transform the MOO problem to SOO or in combination with pareto analysis and evolutionary algorithms. Representative applications in different drug research areas are also discussed.

Expert opinion: Despite their limitations, the use of combined MOO techniques, as well as being complementary to SOO or in conjunction with artificial intelligence, contributes dramatically to efficient drug design, assisting decisions and increasing success probabilities. For multi-target drug design, optimization is supported by network approaches, while applicability of MOO to other fields like drug technology or biological complexity opens new perspectives in the interrelated fields of medicinal chemistry and molecular biology.

By George Lambrinidis & Anna Tsantili-Kakoulidou