Agitation in psychiatric settings, particularly in psychosis, presents a staggering challenge for clinicians, who must both manage the patient's acute symptoms and simultaneously make an accurate diagnosis. Too often, the management of the former confounds the latter. Patients are very often sedated medically, which masks their underlying condition, rendering accurate diagnosis delayed and inherently difficult. Significant data are available regarding both pharmacological and non-pharmacological interventions for agitation that maximise symptom control while minimising confounding side-effects. In this article, a review of the historical evolution of agitation management in psychotic illness is presented, followed by an evidence-based clinical guideline for managing agitation in psychosis in the USA.