This chapter outlines the most important basic principles for the application of high-parametric flow cytometry, with particular attention to the complex relationships between technical components, sample preparation, and staining procedures. The individual subchapters contain selected references, which are recommended as a starting point for a deeper understanding of the respective topics. The complexity of high-parametric flow cytometry is not based on the quantity of parameters alone, but on the planning and the technical implementation, requiring a special focus on small, but important details. If you follow the rules outlined in this chapter and plan as well as validate your experiments accordingly, anyone can utilize and implement high-parametric flow cytometry in their workflow.