Ghana's government has embarked on a decentralization process since the 1980s, but devolution of the health system faces important challenges and weaknesses. Ghana has made significant progress, and several building blocks for a devolved health system have been put in place. However, important weaknesses remain regarding several of the key requirements to successful decentralization. Ghana has along the years put in place several important building blocks for a truly decentralized health system. But these efforts have been hampered, and their effectiveness diminished, by the absence of a strong regulatory and policy framework for health, regulatory conflicts and duplications accumulated by several waves of regulations, weak capacity to coordinate and manage a devolved health system, fragmented management systems regarding staff management, procurement and budgeting and financing. Political instability and the resulting lack of continuity and consistency in the process during most of the period have also prevented the process to take root, and have contributed to the current fragmentation in the health system. International comparisons indicate that Ghana shows a narrow effective decision space with respect to most health functions and sub-functions when compared with several other developing countries. However, taking advantage of the structures and features that have been put in place, strengthening the policy framework, ensuring effective coordination, and addressing the weaknesses highlighted above, could make decentralization of the health system more effective and consistent with GOG general policy.This study analyzes the strengths and weaknesses of the decentralization of the Ghanaian health system and presents a few recommendations and strategies for strengthening the process. It is relevant and timely as the GOG seeks to strengthen and deepen decentralization of the health system; it is also useful for other middle- and low-income countries which are pursuing some form of decentralization of their health system to improve its efficiency and effectiveness.