Evidence-based clinical practice guidelines (EBGs) can provide an invaluable distillation of knowledge regarding best practices based on the available evidence. EBGs, providing accurate and useful guidance to best clinical practices, require a rigorous development process. The American College of Chest Physicians (ACCP) has developed a process that embodies transparency, thoroughness, and timeliness, and effective conflict-of-interest management, and it continues to evolve. This process employs a quantitative and rigorous grading of the strength of recommendations and of the quality of evidence that incorporates sensitivity to health-care resource utilization and patient values and preferences. A review of this process is provided to inform the ACCP membership and those wishing to embark on EBG development.