Severe acute respiratory syndrome coronavirus 2 infection and coronavirus disease 2019 (COVID-19) remain an ongoing public health concern. Although directives are subject to change, nurse practitioners must have a strong working knowledge of COVID-19 precaution and isolation directives to counsel patients on proper implementation of precaution and isolation strategies. This article informs clinicians regarding some input that informs the Centers for Disease Control and Prevention’s COVID-19 isolation directives, provides a review of the most recent directives to symptomatic and asymptomatic patients testing positive for severe acute respiratory syndrome coronavirus 2, discusses the use of the Centers for Disease Control and Prevention’s COVID-19 Isolation and Exposure Calculator; and examines the NP’s role in guiding future research and public health initiatives.