The paper delineates what is seen as key challenges to the chieftaincy institution in Ghana. Historical challenges in the form of colonial attempts to sidestep the institution and the attempts by the immediate post independence governments to subjugate and divest them of their economic strength through drastic laws, never cowed the institution. Currently, the 1992 Fourth Republic Constitution bars chiefs from participating in partisan politics thus infringing on their inalienable right of free association. The responses of chiefs to current challenges include the setting up of education funds, participating in HIV/AIDS education, and sensitizing the people on the dangers of environmental degradation. In sum, the noted resilience of the institution will once more assist in containing the challenges to the institution in the 21st century.