The present paper describes fundamentals, advantages and limitations of the Box-Behnken design (BBD) for the optimization of analytical methods. It establishes also a comparison between this design and composite central, three-level full factorial and Doehlert designs. A detailed study on factors and responses involved during the optimization of analytical systems is also presented. Functions developed for calculation of multiple responses are discussed, including the desirability function, which was proposed by Derringer and Suich in 1980. Concept and evaluation of robustness of analytical methods are also discussed. Finally, descriptions of applications of this technique for optimization of analytical methods are presented.