The world has seen a dramatic rise in the use of unilateral sanctions in recent years. While the uptake of new United Nations sanctions appears to have stabilised, a growing number of countries and regional organisations - spanning advanced and emerging economies - are employing autonomous sanctions in an increasing variety of contexts, for a growing number of objectives and against a mounting range of targets. These shifts come hand-in-hand with multilateralism’s crisis of legitimacy; a shift in US foreign and security policies under the Trump presidency, including the ‘maximum pressure’ campaign and growing use of extraterritorial sanctions. Teemed with wider counterterrorism and anti-money-laundering regulations, this increasingly complex compliance landscape is again having consequential and widely-documented humanitarian impacts, with the Covid-19 pandemic bringing these factors further into the spotlight. This chapter explores likely reasons for these shifts; outlines different types of unilateral sanctions, and examines ramifications of these shifting global sanctions practices.