Cryptococcosis has become a significant public global health problem worldwide. Caused by two species, Cryptococcus neoformans or Cryptococcus gattii, this life-threatening infection afflicts not only immunocompromised individuals but also apparently immunocompetent subjects. Hence, cryptococcosis should no longer be considered merely an opportunistic infection. In this article, we focus on ten unanswered questions/topics in this field with the hope to stimulate discussion and research on these topics that would lead not only to a better understanding of the physiopathology of this disease but also to a better diagnosis and prognosis.