In response to their environment, plants produce upwards of 30 000 phytochemicals that serve to facilitate communication and resistance to abiotic and biotic pressures. With over 3000 plants in commerce and the Nutrition Business Journal reporting 2017 North American sales of 8.35 billion dollars for herbs and botanicals, there is a multitude of products available to consumers. The pace of product innovation far exceeds that of analytical methods development and validation, with new ingredients, matrixes, and combinations resulting in an analytical community that has been unable to keep up. This has led to a lack of validated analytical methods for plant-based health products and to inappropriate method selection where methods do exist. Only after rigorous validation procedures to ensure that methods are fit for purpose should they be used in a routine setting to verify product authenticity and quality. By following systematic procedures and establishing performance requirements for analytical methods before method development and validation, methods can be developed that are both valid and fit for purpose. This chapter summarizes advances in method selection, development, and validation regarding plant-based supplement analysis and provides guidance on best practices for characterization when undertaking pre-clinical and clinical studies.