This article explores the transformations in the regime of practice and discourse concerning chronic mental illness in French psychiatry in the post-war period and the role played by chemotherapy in these transformations. From the 1950s and 60s on, chronicity was reconstructed as a new experience, involving a new set of expectations, of dilemmas and negotiations, and involving new types of actors giving a new meaning to what they were doing with patients. While some psychiatrists thought that neuroleptics could open the way to active treatment of these pathologies, in effect this project faced a series of obstacles: some came from psychiatric ideologies, others from the conditions of psychiatric work. As a result chronicity acquired a new uncertain and elusive shape. Based on an examination of the interplay of meaning and action in psychiatrists’ recourse to neuroleptics in the treatment of their chronic patients, this article seeks to highlight the difficult construction of the idea of chemotherapy in post-war French psychiatry and, more generally, the transformations in its notion of therapy.