With an average prevalence of 25% hypertension is one of the leading chronic diseases in westernized countries. Recent epidemiological data indicate a high proportion of patients with secondary hypertension due to primary aldosteronism that accounts for up to 8–12% of cases. Primary aldosteronism is caused by autonomous secretion of aldosterone by the adrenal cortex which results in hypertension with clinically, biochemically and therapeutically distinct features. With the exception of the small proportion of patients with familial hyperaldosteronism type I, the underlying genetic and molecular basis of this common disease is largely unknown. In this situation mouse models with targeted genetic modification can be utilized to define functional relevance of predefined candidate genes that are known or suspected to be involved in the regulation of aldosterone secretion. Moreover, animal models can aid in the identification of novel gene products that have not yet been identified to play a role in primary aldosteronism. This review will provide a brief overview on the animal models currently available for primary aldosteronism and describe in vivo screening strategies that are likely to provide insight in molecular and genetic mechanisms involved in autonomous aldosterone secretion.