This exploratory article gives a cross-sectional account of how established health-care systems have responded to the novel challenge of drug shortages. In line with previous research, our analysis confirms the existence of strong path dependence in the adoption of policy responses. This path dependence is manifested in a pronounced typology of response patterns where jurisdictional approaches to the management of drug shortages differ along two core dimensions. These are the salience attributed to the problem, and the level to which state organisations engage with the problem. These patterns are mirrored in the conceptual framing and strategic orientation of the respective drug shortage policies, with: Spanish and Irish drug shortage policies focusing on the individual product level and being largely reactive; US policies focusing on the therapeutic level, with a focus on mitigation; and German and Austrian policies seeking to address the active ingredient level, with a proactive focus on shortage prevention. Despite the importance of legacies, we find evidence of innovation and path creation particularly in relation to the US and German approaches, which we explain by the simultaneous occurrence of internal crisis and pressures from local stakeholders. Points for practitioners This article addresses a major challenge, drug shortages, which has emerged in recent years and could be characterised as a ‘system shock’. A typology of policies adopted based on an analysis of a range of health system responses is developed. Fundamental differences across these responses are evident, such as level of action (individual product level/therapeutic level/active ingredient level), time frame (from ad hoc/short term to long term) and strategic approach (reactive/mitigating/preventive). This analysis finds fundamentally different policies, such as delegated institutional powers and census management/network governance. The typology based on the salience attributed to the problem and the nature (proactive/reactive) of policymaking may assist stakeholders in health systems to critique their approach to this challenge and, at a more fundamental level, how the system responds to disruptive events.