An overview of considerations for the development and validation of separation methods used for pharmaceutical quality control is presented. During early development, screening methods using multiple conditions are used to evaluate the significance of predicted impurities and to discover unknown impurities. Once impurities necessary for quality control are identified, methods can be optimized to provide appropriate selectivity, accuracy, precision, detectability, robustness and laboratory efficiency. Numerous computer-aided optimization tools are available for this purpose. The optimized method may be validated according to guidelines under consideration by the International Conference on Harmonization. Validation studies employing statistical experimental design techniques are useful for the determination of method precision and robustness. Examples illustrating the above considerations are provided for high-performance liquid chromatographic methods.