BACKGROUND: Clinical practice guidelines (CPGs) and evidence-based clinical reviews help guide nursing practice. The American Association of Neuroscience Nurses (AANN) has published guidelines for more than 25 years. METHODS: The AANN CPGs are developed using predefined search terms based on PICO (population, intervention, comparison, outcome) questions formulated a priori followed by evaluation of the evidence and creation of recommendations using methodologies of the Grading of Recommendations Assessment, Development, and Evaluation. DISCUSSION: Neuroscience nurses provide care for a specialized population with unique nursing care considerations. The CPG series has been rigorously developed to provide relevant context and practice recommendations to improve this care. CONCLUSION: This article establishes the methodology by which AANN CPGs are developed.