Locked-in Syndrome (LIS) is a rare medical condition with poor prognosis that challenges the notion of recovery for health professionals and for persons that suffer from it and their close relatives. Persons with LIS cannot move (quadriplegia) or speak (anarthria), but they are conscious, cognitively able, can see and hear, and keep bodily sensations. From the onset of the condition and over time, the experience of LIS and its recovery is defined by what I named the certain uncertainty of LIS: very few persons will recover completely whilst other will not at all; in between, different degrees of recovery will vary largely from case to case. This chapter, based on ethnographic material from postdoctoral research on the lived experience of persons with LIS aims to shed light on the paradox of the certain uncertainty of LIS.