In 2017, the Clinical Laboratory Standards Institute (CLSI) approved a proposal for a new guideline to address the validation of assays performed by flow cytometry. Practical instructions are given for pre-examination-phase activities: specimen requirements, reagent evaluation, instrument qualification and standardization, and assay optimization and validation. There is guidance for examination-phase activities such as instrument monitoring and quality-control procedures. Best practices for postexamination activities, such as data review, reporting, storage, and retention, are described. This presentation reviews the key elements of the CLSI proposal and provides real-life examples of how its elements could affect flow cytometry in the laboratory.