Monitoring is a challenging and fundamental issue within planning processes, yet there is little understanding as to whether plans achieved their goals in guaranteeing sustainable development on a territorial level. Follow-up of spatial planning is rather difficult due to insufficient methodologies, deficiencies in plans' contents and resource limitations. The main goal of this research is to develop and test a conceptual framework to support the development of effective indicator based regional spatial plans' (RSPs) monitoring systems. The conceptual framework includes indicators with distinct purposes and has the following features: (i) it establishes links between RSPs, their strategic environmental assessment and monitoring indicators; (ii) it incorporates the contribution of other existing monitoring systems in the regions; and (iii) it defines specific indicator selection criteria. In order to inform the development of the conceptual framework we: (i) review international practice of RSP monitoring; (ii) analyse the features of current Portuguese RSPs; (iii) test the conceptual framework using the RSP and the regional sustainability indicator system of the Algarve region (Portugal) as a case study. Two types of indicators were developed - output/implementation and results/effects - for improving the identification of cause-effect relationships between RSP implementation and associated territorial effects; although this is a continuing challenge, given the strategic nature of RSPs. The usefulness of the conceptual framework was demonstrated in the definition of monitoring indicators for the Algarve's RSP, as well as in the integration of an existing regional sustainability monitoring system.