Sedation is one of the details of ICU care which seems unimportant… until it's not. Over the past decade we've seen a burgeoning repertoire of agents used for sedation and agitated delirium. Unfortunately, the number of medications has out-stripped available Level-I evidence regarding how exactly to use them. This chapter attempts to create a framework for the selection and use of various agents. Looming drug shortages due to COVID-19 may force us to push the envelope, by using different agents in ways which we haven't previously.