Clinical practice guidelines (CPG) make the core of a framework for clinical decision-making. They are intended to optimise healthcare provision and decrease the risk of preventable adverse events or harms. There is strong evidence that the use of guidelines optimises healthcare by discouraging ineffective measures and promoting scientifically proven beneficial interventions. Adherence to guidelines reduces variation and inconsistency in patient care between the different institutions and healthcare providers, creating a framework that could be audited. Guidelines also allow for meaningful involvement of patients in healthcare choices and considers patient preferences and needs. Unfortunately, adherence to national and international clinical practice guidelines is currently sub-optimal globally, therefore the development of clinical practice guidelines must be supported by an effective dissemination and implementation strategy. Guidelines are prepared by multi-disciplinary teams including clinical experts, methodologist, patients’ representatives, public health specialists and health economists. Credible guidelines should be underpinned by systematic reviews of the best available evidence, carefully identifying all relevant studies and judging their scientific strengths and weaknesses. This chapter focuses on some of the key elements of clinical practice guidelines, including quality assessment and key challenges faced by guideline developers globally.