Engaging anticolonial psychiatrists Frantz Fanon and Thomas Adeoye Lambo, this paper explores the relationship between human psychology and decolonization in Africa. Through a close analysis of their clinical works in North and West Africa, the article delineates their respective approach to mental illness, reflecting on issues of culture, method, and knowledge production. The argument put forward is that their perspectives offer important methodological insights that expand and deepen the scope and understanding of decolonization process in Africa. The discussion illuminates that while both thinkers share common critiques about traditional psychiatry they differ on the value and viability of translating Western medical approaches into Africa. This divergence reflects the authors’ historical and critical relation to Western medical epistemology and its colonial legacy. Above all, in exposing key issues and stakes of what is methodologically involved in doing decolonization, it illuminates the irreducibility of both psychic life and translation to effective liberation.