Recent evidence highlights the increasing utilization of guanfacine in the intensive care unit. While dexmedetomidine is a widely used sedative and anti-anxiety agent in the intensive care unit, prolonged use can lead to withdrawal effects when attempting to reduce the dosage. This has generated interest in using guanfacine to manage agitation in patients being weaned off dexmedetomidine. Clonidine has been used for dexmedetomidine weaning, but its use has been associated with adverse cardiovascular events. Some observational studies and case reports have explored the use of guanfacine and have shown its benefits and tolerability for patients taking dexmedetomidine experiencing adverse effects. Guanfacine is increasingly being used in the intensive care unit instead of clonidine and is commonly prescribed for the management of withdrawal effects. While there are limited data from observational studies, it holds promise for future clinical research and broader adoption of guanfacine in the intensive care unit.