Ιn the scenery of the unprecedented global crisis of COVID-19 pandemic, which is still challenging the planet’s social, economic and political limits, the issue of urban and regional resilience to external shocks comes to the forefront as a core property of relevant systems and a distinct feature for effectively coping with unexpected, highly impacting, global and multidimensional (e.g. health, climate change) events. Different reactions to this pandemic, unfolded by countries and cities around the world so far, form a rich canvas of policy responses and provide valuable knowledge and evidence-based results. These are critical for efficaciously confronting the still ongoing COVID-19 repercussions on health, society, economy and political scene. They also establish a lesson-drawing mechanism, enriching thus policy makers’ arsenal, understanding and preparedness towards efficiently dealing with the pandemic, but also other, largely unforeseeable, catastrophic situations. Within such a framework, the present chapter attempts to shed light on policy responses against COVID-19 pandemic in Greece. Given the fact that the management of COVID-19 pandemic is perceived both as an issue of national emergency and respective policy responsibility as well as one affecting mainly urban constellations, work carried out in this chapter is accordingly structured. More specifically, firstly the core policies and the COVID-19-forced ICT reforms, with reference to the national level, are roughly sketched, framing in a way potential responses at the urban level. Secondly, relevant endeavours and policy actions at the urban level are discussed – both as counterparts of national directions and locally driven initiatives – by highlighting efforts in three city examples, namely the cities of Piraeus, Trikala and Larisa. Finally, a critical comparison of COVID-19 policy actions of these cities is carried out in an attempt to identify similarities, city-specific initiatives, linkages/interactions with state policies, and level of mobilization of local communities.