There is a growing medical demand for suitable sedatives and analgesics to support the ongoing progress in diagnostic procedures and imaging techniques. This review provides an update of the pharmacology of the most commonly used drugs used for these procedures and shortly mention new drugs on the horizon.There are many drugs available for procedural sedation; however, they all have drawbacks and shortcomings. Multiple adverse effects are associated with the use of these agents, hence monitoring is essential, and emergency equipment should be readily available. Newer drugs are on the horizon (e.g., remimazolam, fospropofol, and etomidate analogues) with a theoretical more predictable onset and offset; whether these will revolutionize the sedational practice sedation remains unknown.Clinicians should be aware of the pharmacokinetic/pharmacodynamic differences of all agents in order to select appropriate medications for specific procedures and patients.