The aim of this dissertation is to investigate when, why and how regional political leaders initiate secession crises in advanced democracies and under what conditions the unfolding of these crises transforms regional party systems. First, this research shows how regional leaders act strategically and use secession crises to bargain with central governments to extract decentralised powers, to obtain electoral rewards, and less often to pursue idealistic preferences. Secondly, this project finds that regional party systems change substantially when the level of secession crisis is high. The dissertation argues that secession is a more radical territorial demand than the mere defence of regional interests or identity and that it can monopolise public debate. Parties are more likely to compete for the poles of the territorial dimension, but not all are able to adapt their strategies effectively. Secessionist parties and those that support the regional status quo are better prepared and benefit whilst parties located in-between encounter difficulties in either accommodating or dismissing the issue. Consequently, several party system features change. Party competition is transformed from centripetal to centrifugal in the territorial dimension and party cooperation switches from being across the centre-periphery cleavage to become within-block cooperation. Parties with a more heterogeneous composition and with larger size split, factions switch, coalitions are formed, and new parties are created. The fragmentation of the party system and its volatility increase and polarisation in the territorial dimension intensifies. This thesis also shows that citizens modify their territorial preferences to support more regional powers and secession and less regional status quo and recentralising options. These findings are based on a comparative historical analysis of secession crises and party systems in Quebec, the Basque Country, Scotland and Catalonia. While lower crisis levels in the Basque Country and Scotland did not modify their party systems substantially, in Quebec and Catalonia party systems experienced transformations with higher levels of crisis.